Contents

library(gemma.R)
library(data.table)
library(dplyr)
library(ggplot2)
library(ggrepel)
library(SummarizedExperiment)
library(pheatmap)
library(viridis)

1 About Gemma

Gemma is a web site, database and a set of tools for the meta-analysis, re-use and sharing of genomics data, currently primarily targeted at the analysis of gene expression profiles. Gemma contains data from thousands of public studies, referencing thousands of published papers. Every dataset in Gemma has passed a rigorous curation process that re-annotates the expression platform at the sequence level, which allows for more consistent cross-platform comparisons and meta-analyses.

For detailed information on the curation process, read this page or the latest publication.

2 Package cheat sheet

3 Installation instructions

3.1 Bioconductor

You can install gemma.R through Bioconductor with the following code:

if (!require("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

BiocManager::install("gemma.R")

4 Searching for datasets of interest in Gemma

Using the get_datasets function, datasets fitting various criteria can be accessed.

# accessing all mouse and human datasets
get_datasets(taxa = c('mouse','human')) %>% 
    select(experiment.ShortName, experiment.Name,taxon.Name) %>% head
   experiment.ShortName
1:              GSE2018
2:              GSE4523
3:              GSE4036
4:              GSE4034
5:              GSE2866
6:              GSE3253
                                                                                                            experiment.Name
1:                                                                                              Human Lung Transplant - BAL
2:                                                                   Expression Studies of Melanotransferrin in Mouse Brain
3:                                                                                                  perro-affy-human-186940
4:                                                                                                  palme-affy-mouse-198967
5:                                                                                                Donarum-3R01NS040270-03S1
6: Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system
   taxon.Name
1:      human
2:      mouse
3:      human
4:      mouse
5:      mouse
6:      mouse
# accessing human datasets with the word "bipolar"
get_datasets(query = 'bipolar',taxa = 'human') %>% 
     select(experiment.ShortName, experiment.Name,taxon.Name) %>% head
   experiment.ShortName
1:             GSE67645
2:   McLean Hippocampus
3:              byne-cc
4:             GSE45484
5:            GSE134497
6:            GSE160761
                                                                                                                                                                                     experiment.Name
1: Transcriptome dynamics of developing photoreceptors in 3-D retina cultures recapitulates temporal sequence of human cone and rod differentiation revealing cell surface markers and gene networks
2:                                                                                                                                                                                McLean Hippocampus
3:                                                                                                                                              Corpus Callosum data from Stanley collection samples
4:                                        Gene-expression differences in peripheral blood between lithium responders and non-responders in the “Lithium Treatment -Moderate dose Use Study” (LiTMUS)
5:                                                                                                                      Total RNA sequecing for human induced pluripotent derived cerebral organoids
6:                                                            RNA sequencing  in human  iPSCs derived from  bipolar  patients  to identify important therapeutic molecular targets of Valproate(VPA)
   taxon.Name
1:      human
2:      human
3:      human
4:      human
5:      human
6:      human
# access human datasets that were annotated with the ontology term for the
# bipolar disorder

get_datasets(taxa ='human', 
             uris = 'http://purl.obolibrary.org/obo/MONDO_0004985') %>%
    select(experiment.ShortName, experiment.Name,taxon.Name) %>% head
   experiment.ShortName
1:              GSE5389
2:              GSE5388
3:              GSE7036
4:   McLean Hippocampus
5:           McLean_PFC
6:     stanley_feinberg
                                                                                                           experiment.Name
1:           Adult postmortem brain tissue (orbitofrontal cortex) from subjects with bipolar disorder and healthy controls
2: Adult postmortem brain tissue (dorsolateral prefrontal cortex) from subjects with bipolar disorder and healthy controls
3:                                               Expression profiling in monozygotic twins discordant for bipolar disorder
4:                                                                                                      McLean Hippocampus
5:                                                                                                              McLean_PFC
6:                                                                     Stanley consortium collection Cerebellum - Feinberg
   taxon.Name
1:      human
2:      human
3:      human
4:      human
5:      human
6:      human

Note that a single call of these functions will only return 20 results by default and a 100 results maximum, controlled by the limit argument. In order to get all available results, use get_all_pages function on the output of the function

get_datasets(taxa = 'human') %>% 
    get_all_pages() %>% 
    select(experiment.ShortName, experiment.Name,taxon.Name) %>% 
    head()
   experiment.ShortName
1:              GSE2018
2:              GSE4036
3:              GSE3489
4:              GSE1923
5:               GSE361
6:               GSE492
                                                                          experiment.Name
1:                                                            Human Lung Transplant - BAL
2:                                                                perro-affy-human-186940
3: Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis
4: Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells
5:                                                   Mammary epithelial cell transduction
6:                               Effect of prostaglandin analogs on aqueous humor outflow
   taxon.Name
1:      human
2:      human
3:      human
4:      human
5:      human
6:      human

See larger queries section for more details. To keep this vignette simpler we will keep using the first 20 results returned by default in examples below.

The filter parameter of get_datasets allows filtering for datasets with specific properties. A list of such properties can be accessed using filter_properties.

filter_properties()$dataset %>% head
                                      properties    type description
1:                           accession.accession  string        <NA>
2:                    accession.accessionVersion  string        <NA>
3:             accession.externalDatabase.ftpUri  string        <NA>
4:                 accession.externalDatabase.id integer        <NA>
5:        accession.externalDatabase.lastUpdated  string        <NA>
6: accession.externalDatabase.localInstallDbName  string        <NA>

These properties can be used together to fine tune your results

# all datasets with more than 4 samples annotated for any disease
get_datasets(filter = 'bioAssayCount > 4 and allCharacteristics.category = disease')
    experiment.ShortName
 1:              GSE2018
 2:              GSE4036
 3:              GSE2866
 4:              GSE2426
 5:              GSE2867
 6:              GSE3489
 7:              GSE1837
 8:              GSE2178
 9:              GSE1611
10:               GSE857
11:              GSE1294
12:              GSE1070
13:              GSE1069
14:              GSE1068
15:                GSE63
16:                GSE30
17:               GSE466
18:               GSE485
19:               GSE460
20:               GSE492
                                                                                      experiment.Name
 1:                                                                       Human Lung Transplant - BAL
 2:                                                                           perro-affy-human-186940
 3:                                                                         Donarum-3R01NS040270-03S1
 4:                                                           Pre-Neoplastic Stage of Medulloblastoma
 5:                                                                            Zoghbi-5R01NS027699-14
 6:            Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis
 7:                       Comparison of  SNc and VTA dopaminergic neurons. Greene-5P50NS038399-050001
 8:                                                                     Mouse Expression DB 2001 CHMC
 9:                                                   Transcriptome of Ts1Cje and euploids cerebellum
10:                                                                        Triple treatment R6/2 mice
11:                              Expression profile of genes in normal and Down syndrome mouse brains
12:                                                                    2CdA intervention with PK11195
13:                                                                           2.5 mg/kg 2CdA exposure
14:                                                                       2CdA-induced microphthalmia
15:                                                              Brain after ischemia and antioxidant
16: Multiplex three dimensional brain gene expression mapping in a mouse model of Parkinson's disease
17:                                          mRNA expression in regenerated mdx mouse skeletal muscle
18:                                                Genetic basis of sensitivity to pulmonary fibrosis
19:                                                                          Murine dermal burn wound
20:                                          Effect of prostaglandin analogs on aqueous humor outflow
    experiment.ID
 1:             1
 2:             4
 3:             6
 4:            11
 5:            17
 6:            18
 7:            21
 8:            24
 9:            26
10:            31
11:            32
12:            36
13:            37
14:            38
15:            47
16:            49
17:            54
18:            58
19:            99
20:           100
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        experiment.Description
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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Bronchoalveolar lavage samples collected from lung transplant recipients.  Numeric portion of sample name is an arbitrary patient ID and AxBx number indicates the perivascular (A) and bronchiolar (B) scores from biopsies collected on the same day as the BAL fluid was collected.  Several patients have more than one sample in this series and can be determined by patient number followed by a lower case letter.  Acute rejection state is determined by the combined A and B score - specifically, a combined AB score of 2 or greater is considered an acute rejection.
 2:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                Our laboratory has developed the first mouse model overexpressing a RNA-binding protein, the ELAV-like protein HuD, in the CNS under the control of the CaMKinII alpha promoter. Initial behavioral characterization of the mice revealed that they had significant learning deficits together with abnormalities in prepulse inhibition (PPI). At the molecular level, we found that the expression of the growth-associated protein GAP-43, one of the targets of HuD, was increased in the hippocampus of HuD transgenic mice. To characterize these mice further and to evaluate the utility of these animals in understanding human diseases, we propose to use DNA microarray methods. To test our hypothesis we propose 3 specific aims: 1) To characterize the pattern of gene expression in the hippocampus of HuD overexpressor mice 2) To compare the pattern of gene expression in our mouse model with that in the hippocampus of rats prenatally exposed to alcohol (FAS model) and 3) To compare the pattern of gene expression in our mouse model with that shown in post-mortem tissues of patients with schizophrenia. In our previous protocols we examined the pattern of gene expression in our HuD transgenic mice and in rats prenaltally exposed to alcohol. A report by another group (Hakak et al, 2001) showed that three of the HuD targets were upregulated in the prefrontal cortex of patients with schizophrenia. To evaluate whether other target of HuD may be affected in this illness, in the current protocol, we want to compare the pattern of expression in our transgenic mice with in tissue from patients with schizophrenia Based on the behavioral and molecular properties of our HuD transgenic mice we hypothesize that these animals may be good models for the studying the basis of learning disabilities and of diseases that show deficits in PPI such as fetal alcohol syndrome and schizophrenia. All 28 samples are derived from cerebellar tissues for patients with schizophrenia and matched controls.  The specimens were obtained from the Maryland Brain Collection according to NIH guidelines for confidentially and privacy. The protocol used in these studies was reviewed by our HRRC which found that our studies do not fall within the category of protocols monitored by the IRB (see attached letter form the HRRC). Specimens from 14 patients with a diagnosis of schizophrenia performed according to DSM-IV criteria and 14 sex-, age- and PMI-matched controls was included in this study. No differences were found between patients and control subjects in the average age (45±12 versus 43±10 years, p=0.86) or PMI (12±5 versus 16±6 hours, p=0.11). We will provide 28 samples containing 5 ug of RNA each in DEPC water (see validation of the quality of the RNA below). In addition, we include in our study animals treated with haloperidol as control for medication. These samples will be submitted in a separate protocol.\nDate GSE4036 Last Updated: Jan 13 2006\nContributors:  Nora I Perrone-Bizzozero\nIncludes GDS1917.\n Update date: Jun 14 2006.\n Dataset description GDS1917: Analysis of cortical samples corresponding to the crus I/VIIa area of the cerebellum from schizophrenia patients. A study indicates that targets of the RNA-binding ELAV-like protein HuD are overexpressed in the prefrontal cortex of patients with schizophrenia.
 3:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Succinate semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder effecting approximately 350 people around the world. Patients suffering from SSADH deficiency experience language acquisition failure, memory deficiencies, autism, increased aggressive behaviors, and seizures. There is a chemical buildup of both gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB) in the neurological system of these patients. The Aldh5a1-/- knock out mouse model of SSADH deficiency shows the same chemical imbalances as the human disease, with additional fatal tonic-clonic seizures at three weeks of age.  The elucidation of seizure causing pathways will facilitate treatment of seizure phenotypes in diseases with related epilepsy. Gene expression patterns within the hippocampus, cerebellum, and cortex of SSADH deficient mice (Aldh5a1-/- mice) will be compared to wild type mice at a time point immediately prior to fatal seizures. We hypothesis that the SSADH deficient mice experience a dysfunction of glutamate/GABA/ glutamine neurotransmitter cycle linked to astroglial metabolism and/or uptake of neuronally-released glutamate. The increased levels of GHB and GABA lead to down regulation of GABA-B-Receptor leading to seizures. The SSADH deficient phenotype may also be caused by ongoing oxidative damage and the pathological role of succinic semialdehyde. SSADH deficient mice (Aldh5a1-/- knock out) exhibit fatal seizures around three weeks of age. Mutant and wild type mice will be sacrificed between 17 and 19 days of life, and brain sections will be extracted and frozen (using a standard protocol). Hippocampus, cerebellum, and cortex from three mutant mice and three wild type mice will individually be expression profiled on the Affymetrix platform, giving a total of eighteen arrays. Comparative analysis will then be carried out, evaluating the transcript differences between mutant and wild type mice in each brain region.\nDate GSE2866 Last Updated: Jun 08 2006\nContributors:  E A Donarum\nIncludes GDS1745.\n Update date: Jun 08 2006.\n Dataset description GDS1745: Analysis of brain hippocampi, cerebella, and cortices of succinate semialdehyde dehydrogenase (SSADH)-deficient mutants at 3 weeks of age, when fatal seizures occur. Results indicate that SSADH deficiency results in the dysregulation of genes involved in myelin structure and compaction.
 4: SUMMARY  Medulloblastoma is the most common malignant brain tumor in children. It is thought to result from transformation of granule cell precursors (GCPs) in the developing cerebellum, but little is known about the early stages of the disease. Here we identify a pre-neoplastic stage of medulloblastoma in patched heterozygous mice, a model of the human disease. We show that pre-neoplastic cells are present in the majority of patched mutants, although only 16% of these mice develop tumors. Pre-neoplastic cells, like tumor cells, exhibit activation of the Sonic hedgehog pathway and constitutive proliferation. Importantly, they also lack expression of the wild-type patched allele, suggesting that loss of patched is an early event in tumorigenesis. While pre-neoplastic cells resemble GCPs and tumor cells in many respects, they have a distinct molecular signature. Genes that mark the pre-neoplastic stage include regulators of migration, apoptosis and differentiation, processes critical for normal development but previously unrecognized for their role in medulloblastoma. The identification and molecular characterization of pre-neoplastic cells provides insight into the early steps in medulloblastoma formation, and may yield important markers for early detection and therapy of this disease.  ANIMALS  Patched heterozygous mice (Goodrich et al., 1997) were obtained from Matthew Scott?s lab at Stanford, and maintained by breeding with 129X1/SvJ mice from Jackson Laboratories. Math1-GFP transgenic mice (Lumpkin et al., 2003) were provided by Jane Johnson at UT Southwestern Medical Center. Math1-GFP/patched+/- mice were generated by crossing patched heterozygotes with Math1-GFP mice, and then backcrossing to Math1-GFP mice three times before further analysis. All mice were maintained in the Cancer Center Isolation Facility at Duke University Medical Center.  ISOLATION OF CELLS  Granule cell precursors (GCPs) were isolated from 7-day-old (P7) patched+/- mice; preneoplastic cells were obtained from 6 week-old patched mutants; and tumor cells were obtained from 10-25-week old patched mutants displaying physical and behavioral signs of medulloblastoma. Cells were isolated from each source using a protocol described in (Wechsler- Reya and Scott, 1999). Briefly, cerebella were digested in solution containing 10 U/ml papain Oliver et al. Pre-Neoplastic Stage of Medulloblastoma - 8 - (Worthington, Lakewood, NJ) and 250 U/ml DNase (Sigma) and triturated to obtain a cell suspension. This suspension was centrifuged through a step gradient of 35% and 65% Percoll (Amersham Biosciences, Piscataway, NJ), and cells were harvested from the 35%-65% interface. Cells were resuspended in serum-free culture medium consisting of Neurobasal containing B27 supplement, sodium pyruvate, L-glutamine, and penicillin/streptomycin (all from Invitrogen, Carlsbad, California) and counted on a hemacytometer. Cells used for RNA isolation were centrifuged and flash frozen in liquid nitrogen. For proliferation assays or immunostaining, cells were plated on poly-D-lysine (PDL)-coated tissue culture vessels and incubated in serum-free culture medium.  MICROARRAY HYBRIDIZATION AND ANALYSIS  RNA from GCPs, pre-neoplastic cells and tumor cells (isolated as described above, but not FACS-sorted) and from normal adult cerebellum (not dissociated) was converted to cDNA using the Superscript Choice cDNA kit (Invitrogen) and a T7-dT(24) primer (Genset/Proligo, Boulder, CO). cRNA was generated using a T7-transcription/labeling kit from Enzo Life Sciences and hybridized to Affymetrix U74Av2 chips (Affymetrix, Santa Clara, CA). Chips were scanned, and hybridization data were acquired using Affymetrix Suite 5.0 software. Affymetrix CEL files were normalized and quantified using Bioconductor software with the gcRMA model to quantify gene expression levels (Gentleman and Carey, 2002). Unsupervised principal components analysis (PCA) was used to identify the relationships among normal adult cerebellum, GCPs, pre-neoplastic cells and tumor cells based on expression profiles. To identify genes that were differentially expressed among GCPs, pre-neoplastic cells and tumor cells, supervised analysis was carried out. A gene-by-gene ANOVA model with three groups (GCP, pre-neoplastic, tumor) was used to fit the log2-transformed intensities. To correct for multiple comparisons, the nominal p-value was adjusted using the false discovery rate (Benjamini and Hochberg, 1995). Genes were considered to be differentially expressed if they satisfied all of the following criteria: a difference in expression greater than 1.9-fold between any two groups, a maximum absolute intensity difference larger than 32 units, and an adjusted pvalue < 0.01. There were 118 genes that met these criteria. The identities of differentially expressed genes were verified by integrating data from the Affymetrix and Unigene databases. Gene functions were determined using information from Gene Ontology, Unigene, LocusLink and PubMed databases. Clustering was performed with Cluster and Treeview (Eisen et al., 1998). All statistical analysis was performed using R-1.7 software (Dalgaard, 2002). Results were visualized with Spotfire 6.0 (Somerville, MA).  CORRESPONDING AUTHOR  Robert J. Wechsler-Reya* Dept. of Pharmacology & Cancer Biology, Duke University Medical Center Box 3813, Durham, NC 27710 Phone: 919-613-8754. Fax: 919-668-3556. Email: rw.reya@duke.edu.\nDate GSE2426 Last Updated: Oct 28 2005\nContributors:  R J Wechsler-Reya Trang T Huynh Simon M Lin Jonathan F Wells Tracy A Read Anriada Mehmeti Jessica D Kessler Robert J Wechsler-Reya Trudy G Oliver\nIncludes GDS1110.\n Update date: May 09 2005.\n Dataset description GDS1110: Analysis of granule cell precursors, pre-neoplastic cells, and tumor cells obtained from 7 day old, 6 week old, and 10 to 25 week old patched heterozygous animals, respectively. Results provide insight into the mechanisms of pathogenesis of medulloblastoma at the early stage.
 5:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        A number of human neurodegenerative diseases result from the expansion of a glutamine repeat within the disease-causing protein. Spinocerebellar ataxia type1 is one such disease, caused by expansion of a polyglutamine tract in the novel protein ataxin-1. To faithfully model SCA1 in the mouse, we generated  knock-in mice carrying 154 CAG repeats in the mouse Sca1 locus. These mice reproduced many aspects of the human disease. Despite ubiquitous expression of the mutant protein, they developed slowly progressive selective neurodegeneration , which is most distinct in Purkinje cells and spinal cord. Alterations in gene expression have been proposed to be involved in the pathogenesis of polyglutamine disease including SCA1, but the changes of gene expression in an authentic disease model have not been characterized. We believe that knowledge of these genes will give insight into the pathophysiology of SCA1 and may ultimately be relevant to the treatment of SCA1. We will determine gene expression patterns in the cerebellum and forebrain at three different time points. We propose that the genes whose expression is affected  by mutant ataxin-1 expression are effectors for neuronal dysfunction and neuronal degeneration in the knock-in mice. We also hypothesize the difference in the expression levels of these genes accounts for selective vulnerability of neurons. We will examine three time points: 4 weeks, 11 weeks, and 20 weeks of age. We have shown that the mice developed motor incoordination as revealed  by rotating rod test as early as 5 weeks of age but it was not until 10 weeks that they start showing clear  neurological  phenotype such as clasping.  At each point, we will compare the pattern between the mutant and wild-type littermate. Animals will be prepared and sacrificed by a standard procedure. Cerebellum and spinal cord are the most affected areas whereas forebrain shows less neurodegeneration. Tissue will be rapidly dissected from cerebellum and forebrain, frozen in liquid nitrogen, and stored at ?80 C until analysis. Tissues will be sent to the centers (as opposed to RNA). We will be providing 9 tissue samples from three litters for each time point to mitigate any expression differences resulting from subtle differences of procedure or environment where the mice grow.\nDate GSE2867 Last Updated: Jul 06 2005\nContributors:  H Zoghbi\nIncludes GDS1756.\n Update date: May 02 2006.\n Dataset description GDS1756: Analysis of cerebellum and forebrain tissue of knock-in mice carrying 154 CAG repeats in the spinocerebellar ataxia type 1 (SCA1) locus at 4 and 12 weeks of age. Results provide insight into the pathophysiology of the neurodegenerative disease SCA1.
 6:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             The neurodegenerative process in HIV encephalitis (HIVE) is associated with extensive damage to the dendritic and synaptic structure that often leads to cognitive impairment. Several mechanisms might be at play, including release of neurotoxins, oxidative stress and decreased activity of neurotrophic factors. Furthermore, HIV-mediated dysregulation of genes involved in neuronal maintenance might play an important role. For this purpose, cRNA was prepared from the brains of 17 AIDS patients for analysis with the Affymetrix Human U95Av2 GeneChip and analyzed with the GeneSpring Expression Analysis Software. Out of 12,625 genes analyzed, 74 were downregulated and 59 were upregulated compared to controls. Initial alternative analysis of RNA was performed by ribonuclease protection assay (RPA). In cases with HIVE, downregulated genes included neuronal molecules involved in synaptic plasticity and transmission (ion channels, synaptogyrin, synapsin II), cell cycle (p35, p39, CDC-L2, CDC42, PAK1) and signaling molecules (PI3K, Ras-Raf-MEK1), transcription factors and cytoskeletal components (MAP-1B, MAP-2, tubulin, adducin-2). Upregulated genes included those involved in neuroimmune (IgG, MHC, ?2microglobulin) and anti-viral responses (interferon-inducible molecules), transcription (STAT1, OLIG2, Pax-6) and signaling modulation (MEK3, EphB1) of the cytoskeleton (myosin, aduccin-3, radixin, dystrobrevin). Taken together, this study suggests that HIV proteins released from infected macrophages might not only induce a neuroinflammatory response, but also may promote neurodegeneration by interfering with neuronal transcription of genes involved in regulating signaling and cytoskeletal molecules important in maintaining synapto-dendritic functioning and integrity.\nDate GSE3489 Last Updated: Mar 07 2006\nContributors:  Eleanor S Roberts Dianne Langford Anthony Adame Edward Rockenstein Leslie Crews Howard S Fox Eliezer Masiliah Ian Everall\nIncludes GDS1726.\n Update date: May 30 2006.\n Dataset description GDS1726: Analysis of brain frontal cortex of HIV-seropositive patients with HIV encephalitis (HIVE). HIVE affects >40% of AIDS patients, promoting neurodegeneration and cognitive impairment. Results suggest HIV-mediated dysregulation of genes involved in neuronal maintenance might play an important role.
 7:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     The cardinal clinical features of Parkinson's disease (PD) (rigidity, rest tremor, bradykinesia, and postural instability) result from selective loss of midbrain dopaminergic neurons.  More specifically, dopaminergic neurons in the substantia nigra pars compacta (SNc) are much more susceptible to damage than the adjacent dopaminergic neurons in the ventral tegmental area (VTA).  This dichotomy is not only seen in human Parkinsons disease, but also in many animal models of PD, including administration of the mitochondrial toxin rotenone to rats, which replicates many of the behavioral and neuropathological features of PD.  The factors underlying this selective vulnerability are unknown, but could be related to differences in neuronal circuitry, differences in glial support, or intrinsic differences between the neuronal populations of the two regions.  Elucidation of these factors may lead to a greater understanding of the pathogenesis and treatment of Parkinson's disease. We will determine gene expression profiles of untreated rat SNc and VTA dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA. There are intrinsic differences in gene expression between dopaminergic neurons in the rat SNc and VTA that result in greater susceptibility of SNc neurons to degeneration in experimental parkinsonism.  These differences may be related to dopamine metabolism, oxidative metabolism and stress, protein aggregation, or other unforseen pathways. We will compare gene expression profiles between SNc and VTA dopaminergic neurons in normal rats.  No treatment or time points will be studied in this experiment.  Animals will be anesthetized, sacrificed by decapitation, and brains frozen on dry ice.  Frozen sections will be collected onto glass microscope slides and rapidly immunostained for tyrosine hydroxylase to identify dopaminergic neurons.  SNc and VTA neurons (approx. 200 per sample) will be isolated using laser capture microscopy.  Total RNA will be extracted and poly-A RNA will be amplified using a modified Eberwine protocol.  aRNA will be sent to the centers for labeling and hybridization to Affymetrix rat U34A arrays.  We have confirmed with the center that our aRNA protocol is compatible with the centers amplification protocols; in fact, it is essentially identical.  We will be providing a two-round amplification product to the center for labeling and hybridization.  We recognize that using RNA after three rounds of amplification  may decrease sensitivity for low copy number transcripts, but favor this approach versus pooling our samples (which are inherently paired) at this point.  We have discussed this point in detail with the center. SNc and VTA samples from eight animals (16 samples total) will be provided to mitigate differences specific to individual animals.  With the assisatnce of the center, paired t-tests will be used to determine differential expression between the two regions.  Permutational t-test analysis and/or Benjamini and Hochberg analysis of expression ratios will be used to protect against multiple comparisons.  Selected differentially expressed genes will be validated on separate tissue samples using quantitative RT-PCR or in situ hybridization.\nDate GSE1837 Last Updated: Feb 02 2006\nContributors:  James G Greene\nIncludes GDS1641.\n Update date: Jun 08 2006.\n Dataset description GDS1641: Analysis of dopaminergic neurons of the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) from normal animals. SNc dopaminergic neurons are more susceptible to degeneration in Parkinson's disease than VTA dopaminergic neurons.
 8:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Expression profiles of different mouse tissue samples profiles.\nDate GSE2178 Last Updated: May 29 2005\nContributors:  Michael Mucenski Bruce J Aronow Belinda Peach Mitchell Cohen Amy Moseley Susan E Waltz John Maggio Sandra Degen Steve Potter Thomas Doetschman Chris Erwin Joanna A Groden James Lessard Linda Parysek R Hirsch MaryBeth Genter Jianhua Zhang Kathleen Anderson Jonathan D Katz John Dedman Michael Lehman Jorge A Bezerra Michael D Bates Ming Xu Dan Wiginton Jeff A Molkentin\nIncludes GDS1322.\n Update date: Nov 09 2005.\n Dataset description GDS1322: Gene expression profiles across a wide variety of tissue samples. The tissues examined include nervous system, skeletal muscle, male and female reproductive organs, gastrointestinal tract, as well as organs in a developmental context including lung, liver, kidney, and heart.
 9:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Transcriptome analysis of Ts1Cje (mouse model of Down syndrome) and euploids murine cerebellum during postnatal development.\nDate GSE1611 Last Updated: Mar 27 2006\nContributors:  Randal Moldrich Isabelle Rivals Pierre-Marie Sinet Stylianos E Antonarakis Robert Lyle Geoffroy Golfier Luce Dauphinot Laurence Ettwiller Kiyoko Toyama Charles J Epstein Léon Personnaz Maire-Claude Potier Minh Tran Dang Jean Rossier\nIncludes GDS994.\n Update date: Jan 11 2005.\n Dataset description GDS994: Expression profiling of brain cerebella from Ts1Cje males at postnatal days 0, 15, and 30.  RNA pooled from 3 males at each developmental stage. Results provide insight into the molecular changes contributing to the pathogenesis of Down syndrome.
10:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Huntington?s disease is a genetic disease caused by a single mutation. It is characterised by progressive movement, emotional and cognitive deficits. R6/2 transgenic mice carrying the Huntington?s disease mutation have a progressive neurological phenotype, including deterioration in cognitive function. The mechanism underlying the cognitive deficits in R6/2 mice is unknown, but dysregulated gene expression, reduced neurotransmitter levels and abnormal synaptic function are present before the cognitive decline becomes pronounced. Our goal here was to ameliorate the cognitive phenotype in R6/2 mice using a combination drug therapy (tacrine, moclobemide and creatine) aimed boosting neurotransmitter levels in the brain. Treatment from 5 weeks of age prevented deterioration in two different cognitive tasks until at least 12 weeks. However, motor deterioration continued unabated. Microarray analysis of global gene expression revealed that many genes significantly up- or down-regulated in untreated R6/2 mice had returned towards normal levels after treatment. Thus dysregulated gene expression was reversed by the combination treatment in the R6/2 mice and probably underlies the observed improvements in cognitive function. Our study shows that cognitive decline caused by a genetic mutation can be slowed by a combination drug treatment, and gives hope that cognitive symptoms in HD can be treated.\nDate GSE857 Last Updated: Dec 21 2005\nContributors:  Angela K Hodges Lesley Jones Paul D Lewis A J Morton Stephen B Dunnett Mark J Hunt\nIncludes GDS717.\n Update date: Sep 09 2004.\n Dataset description GDS717: Whole brain hemispheres from Huntingtons disease model R6/2 transgenic mice treated with creatine, tacrine and moclobemide from 5 weeks of age. Drug therapy was aimed at boosting neurotransmitter levels and improve cognitive functions.
11:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.\nDate GSE1294 Last Updated: May 29 2005\nContributors:  Kazuhiro Yamakawa\nIncludes GDS682.\n Update date: Nov 22 2004.\n Dataset description GDS682: Analyses of six Ts1Cje (Down syndrome) and six normal brains at postnatal day 0. Dosage-dependent over-expression of genes in trisomic region of Ts1Cje observed.\nIncludes GDS681.\n Update date: Nov 22 2004.\n Dataset description GDS681: Analyses of six Ts1Cje (Down syndrome) and six normal brains at postnatal day 0. Dosage-dependent over-expression of genes in trisomic region of Ts1Cje observed.
12:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        In this time course pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Exposed embryos were co-treated with PK11195, a nontoxic ligand of the mitochondrial peripheral-type benzodiazepine receptor (Bzrp) that effectively blocks p53 protein induction and developmental toxicity induced with 2CdA. Sampling intervals were anchored to the conditional biomarker (p53 protein induction) expressed in 2CdA-treated embryos between 3.0- and 4.5h post-exposure. Since p53 protein induction has been defined as a critical event in 2CdA-induced microphthalmia, these sampling intervals represent times before (3.0h), during (4.5h), and after (6.0h) this critical event. No p53 induction is observed in embryos co-treated with 2CdA and PK11195. All measurements were on RNA from the embryonic headfold.\nDate GSE1070 Last Updated: May 29 2005\nContributors:  Jeffrey H Charlap Thomas B Knudsen Amar V Singh Kimberly R Nemeth\nIncludes GDS632.\n Update date: Jul 14 2004.\n Dataset description GDS632: Temporal analysis of ocular teratogen 2-chloro-2'deoxyadenosine (2CdA) exposure in developing embryos, intervention with PK11195, and induction of microphthalmia (small eye syndrome). Embryonic headfold examined at 3, 4.5, and 6 hours.
13:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                In this time course pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Sampling intervals were anchored to the conditional biomarker (p53 protein induction) expressed in 2CdA-treated embryos between 3.0- and 4.5h post-exposure. Since p53 protein induction has been defined as a critical event in 2CdA-induced micropthalmia, these sampling intervals represent times before (3.0h), during (4.5h), and after (6.0h) this critical event. All measurements were on RNA from the embryonic headfold.\nDate GSE1069 Last Updated: May 29 2005\nContributors:  Kimberly R Nemeth Jeffrey H Charlap Amar V Singh Thomas B Knudsen\nIncludes GDS631.\n Update date: Jul 14 2004.\n Dataset description GDS631: Temporal analysis of ocular teratogen 2-chloro-2'deoxyadenosine (2CdA) exposure and induction of microphthalmia (small eye syndrome). Pregnant 8 days post coitum CD-1 dams exposed to 2.5 mg/kg 2CdA, and embryonic headfold examined at 3, 4.5, and 6 hours.
14:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  In this dose series pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. Test doses were developed from a teratological series for 2CdA-induced microphthalmia using BMDS modeling software from the US EPA. Benchmark doses for microarray analysis were: 5.0 mg/kg (25% risk), 2.5 mg/kg (5% risk), 1.25 mg/kg (NOAEL), and 0.625 mg/kg (subNOAEL). All measurements were on RNA from the embryo proper at 3.0h post-treatment.\nDate GSE1068 Last Updated: May 29 2005\nContributors:  Jeffrey H Charlap Kimberly R Nemeth Amar V Singh Thomas B Knudsen\nIncludes GDS630.\n Update date: Jul 13 2004.\n Dataset description GDS630: Dose response analysis of ocular teratogen 2-chloro-2'deoxyadenosine (2CdA) exposure and induction of microphthalmia (small eye syndrome). Pregnant 8 days post coitum CD-1 dams exposed to 5, 2.5, 1.25 or 0.625 mg/kg 2CdA, and embryos examined at 3 hours.
15:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                A catalytic antioxidant (AEOL 10150) attenuates expression of inflammatory genes in stroke.  White and grey matter in the distribution on the middle cerebral artery 6 hours after administration of the saline/catalytic antioxidant AEOL 10150 and ischemia/reperfusion of the MCAO; pooled mRNA from 6 brains.\nDate GSE63 Last Updated: Jul 18 2005\nContributors:  David S Warner James D Crapo Robert D Pearlstein Huaxin Sheng Russell P Bowler Jan J Enghild\nIncludes GDS55.\n Update date: Apr 09 2003.\n Dataset description GDS55: C57BL/6J mice subjected to 60 min of right middle cerebral artery occlusion (MCAO). Catalytic antioxidant AEOL 10150 given 5 m after onset of reperfusion. After 6 h, MCA parenchyma harvested. Found AEOL 10150 attenuates immune response.
16:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Voxelation is a novel technology designed to produce high throughput, three-dimensional imaging of gene expression patterns in the brain. In these experiments, mouse brains were dissected into 40 voxels, or cubes, by cutting 10 serial coronal sections and transecting each coronal section into fourths. Using microarrays, the gene expression pattern of 9000 genes was acquired for both a normal and a pharmacological model of Parkinson's disease (PD) mouse brain. The mice used in these experiments were C57BL/6J males 10-24 weeks in age.\nDate GSE30 Last Updated: May 29 2005\nContributors:  Simon Yee Alex Ossadtchi Richard M Leahy Vanessa M Brown Arshad H Khan Desmond J Smith William P Melega Simon R Cherry\nIncludes GDS22.\n Update date: Mar 22 2004.\n Dataset description GDS22: Generation of a three-dimensional brain gene expression patterns for both normal brain and a pharmacological model of Parkinson's disease. Networks of anatomically coregulated genes defined.
17:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), beta-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.\nDate GSE466 Last Updated: Jun 15 2005\nContributors:  P Zhao E P Hoffman B S Tseng J A Granchelli S E Gordon L C Folk F W Booth J S Pattison R W Madsen\nIncludes GDS236.\n Update date: Jun 26 2003.\n Dataset description GDS236: Examination of mdx mouse, Duchenne muscular dystrophy model. 16 week regenerating mdx muscle analyzed in search for salvage pathways that maintain skeletal muscle integrity in the absence of functional dystrophin protein.
18:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         The murine pulmonary response is strain specific.  Susceptible strains such as C57BL6/J experience an inflammatory response followed by progressive lung disease.  Resistant strains such as Balb/c do not experience significant degrees of inflammation or fibrosis.  This study aims to determine the genetic basis of sensitivity differences between strains.\nDate GSE485 Last Updated: Jul 27 2006\nContributors:  David   Moller Y W Chen\nIncludes GDS251.\n Update date: Jun 27 2003.\n Dataset description GDS251: Determination of genetic basis of sensitivity to pulmonary fibrosis induced by bleomycin by comparing susceptible (C57BL6/J) and resistant (Balb/c) strains. C57BL6/J experience inflammatory response then progressive lung disease, Balb/c do not.
19:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Investigation into murine dermal burn wound. Mouse thermal injury induced, and skin excised at 0 hours, 2 hours, 3 days and 14 days post-injury.\nDate GSE460 Last Updated: Jun 15 2005\nContributors:  David W Mozingo Robert J Feezor Lyle L Moldawer Heather N Paddock Juan C Varela Gregory S Schultz Henry V Baker\nIncludes GDS353.\n Update date: Jun 23 2003.\n Dataset description GDS353: Investigation into dermal burn wound healing. Thermal dermal injury induced. Skin excised at 0 hours, 2 hours, 3 days and 14 days post-injury.
20:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    The purpose of this study is to discover genes that might increase aqueous humor outflow when human ciliary muscle or human trabecular meshwork cells are treated with the prostaglandin analogues latanoprost free acid or prostaglandin F2alpha. Five tissue donors were pooled on each chip.\nDate GSE492 Last Updated: Jul 27 2006\nContributors:  Paul   Russell\nIncludes GDS359.\n Update date: Apr 14 2004.\n Dataset description GDS359: Glaucoma study investigating molecular basis of increase in aqueous humor outflow when human ciliary muscle or human trabecular meshwork cells are treated with prostaglandin analogs latanoprost free acid or prostaglandin F2alpha.
    experiment.Troubled experiment.Accession experiment.Database
 1:               FALSE              GSE2018                 GEO
 2:               FALSE              GSE4036                 GEO
 3:               FALSE              GSE2866                 GEO
 4:               FALSE              GSE2426                 GEO
 5:               FALSE              GSE2867                 GEO
 6:               FALSE              GSE3489                 GEO
 7:               FALSE              GSE1837                 GEO
 8:               FALSE              GSE2178                 GEO
 9:               FALSE              GSE1611                 GEO
10:               FALSE               GSE857                 GEO
11:               FALSE              GSE1294                 GEO
12:               FALSE              GSE1070                 GEO
13:               FALSE              GSE1069                 GEO
14:               FALSE              GSE1068                 GEO
15:               FALSE                GSE63                 GEO
16:               FALSE                GSE30                 GEO
17:               FALSE               GSE466                 GEO
18:               FALSE               GSE485                 GEO
19:               FALSE               GSE460                 GEO
20:               FALSE               GSE492                 GEO
                      experiment.URI experiment.SampleCount
 1: http://www.ncbi.nlm.nih.gov/geo/                     34
 2: http://www.ncbi.nlm.nih.gov/geo/                     28
 3: http://www.ncbi.nlm.nih.gov/geo/                     18
 4: http://www.ncbi.nlm.nih.gov/geo/                     14
 5: http://www.ncbi.nlm.nih.gov/geo/                     20
 6: http://www.ncbi.nlm.nih.gov/geo/                     28
 7: http://www.ncbi.nlm.nih.gov/geo/                     15
 8: http://www.ncbi.nlm.nih.gov/geo/                    161
 9: http://www.ncbi.nlm.nih.gov/geo/                     12
10: http://www.ncbi.nlm.nih.gov/geo/                     13
11: http://www.ncbi.nlm.nih.gov/geo/                     24
12: http://www.ncbi.nlm.nih.gov/geo/                      6
13: http://www.ncbi.nlm.nih.gov/geo/                      6
14: http://www.ncbi.nlm.nih.gov/geo/                      8
15: http://www.ncbi.nlm.nih.gov/geo/                     17
16: http://www.ncbi.nlm.nih.gov/geo/                     80
17: http://www.ncbi.nlm.nih.gov/geo/                     10
18: http://www.ncbi.nlm.nih.gov/geo/                     24
19: http://www.ncbi.nlm.nih.gov/geo/                     12
20: http://www.ncbi.nlm.nih.gov/geo/                     12
    experiment.LastUpdated
 1:    2023-09-25 18:33:39
 2:    2023-09-25 17:16:22
 3:    2023-09-25 17:26:29
 4:    2023-09-18 20:32:07
 5:    2023-09-18 21:15:13
 6:    2023-10-03 19:39:07
 7:    2022-08-16 16:43:25
 8:    2023-10-03 19:39:08
 9:    2022-08-12 14:03:02
10:    2023-09-07 21:19:21
11:    2023-01-11 22:51:30
12:    2022-08-22 17:33:27
13:    2022-08-25 17:03:34
14:    2022-08-19 17:00:44
15:    2023-09-07 21:20:47
16:    2022-08-22 17:52:37
17:    2022-08-30 18:37:23
18:    2022-08-25 17:24:31
19:    2023-09-07 21:22:40
20:    2022-08-22 19:09:36
                                          experiment.batchEffect
 1:                                      NO_BATCH_EFFECT_SUCCESS
 2:                                         SINGLE_BATCH_SUCCESS
 3: This data set may have a batch artifact (PC 2), p=0.00064920
 4:                                      NO_BATCH_EFFECT_SUCCESS
 5:                                         SINGLE_BATCH_SUCCESS
 6:                                                NO_BATCH_INFO
 7:                                      BATCH_CORRECTED_SUCCESS
 8:                                                NO_BATCH_INFO
 9:                                      BATCH_CORRECTED_SUCCESS
10:                                                NO_BATCH_INFO
11:                                      NO_BATCH_EFFECT_SUCCESS
12:                                                NO_BATCH_INFO
13:                                                NO_BATCH_INFO
14:                                                NO_BATCH_INFO
15:                                                NO_BATCH_INFO
16:                                                NO_BATCH_INFO
17:                                         SINGLE_BATCH_SUCCESS
18:  This data set may have a batch artifact (PC 1), p=0.0054886
19:                                                NO_BATCH_INFO
20:                                      BATCH_CORRECTED_SUCCESS
    geeq.batchCorrected geeq.batchConfound geeq.batchEffect geeq.rawData
 1:               FALSE                  1                1            1
 2:               FALSE                  1                1            1
 3:               FALSE                 -1                0            1
 4:               FALSE                  1                1            1
 5:               FALSE                  1                1            1
 6:               FALSE                  0                0           -1
 7:                TRUE                  1                1            1
 8:               FALSE                  0                0           -1
 9:                TRUE                  1                1            1
10:               FALSE                  0                0           -1
11:               FALSE                  1                0           -1
12:               FALSE                  0                0           -1
13:               FALSE                  0                0           -1
14:               FALSE                  0                0           -1
15:               FALSE                  0                0           -1
16:               FALSE                  0                0           -1
17:               FALSE                  1                1            1
18:               FALSE                 -1                0            1
19:               FALSE                  0                0           -1
20:                TRUE                  1                1            1
    geeq.qScore geeq.sScore taxon.Name  taxon.Scientific taxon.ID taxon.NCBI
 1:   0.9976341      0.8750      human      Homo sapiens        1       9606
 2:   0.9971246      0.7500      human      Homo sapiens        1       9606
 3:   0.4273933      0.6875      mouse      Mus musculus        2      10090
 4:   0.8558619      0.6875      mouse      Mus musculus        2      10090
 5:   0.8469065      0.6250      mouse      Mus musculus        2      10090
 6:   0.4098798      0.5000      human      Homo sapiens        1       9606
 7:   0.9979230      0.3125        rat Rattus norvegicus        3      10116
 8:  -0.2259327      0.0625      mouse      Mus musculus        2      10090
 9:   0.8565754      0.6875      mouse      Mus musculus        2      10090
10:   0.2789180      0.1875      mouse      Mus musculus        2      10090
11:   0.8548596      0.3125      mouse      Mus musculus        2      10090
12:  -0.1476548     -0.1625      mouse      Mus musculus        2      10090
13:  -0.1473691     -0.1625      mouse      Mus musculus        2      10090
14:  -0.1431355     -0.1625      mouse      Mus musculus        2      10090
15:   0.2694997      0.1875      mouse      Mus musculus        2      10090
16:  -0.1072255      0.0625      mouse      Mus musculus        2      10090
17:   0.7132509      0.6875      mouse      Mus musculus        2      10090
18:   0.4256551      0.5625      mouse      Mus musculus        2      10090
19:   0.2689840      0.4375      mouse      Mus musculus        2      10090
20:   0.8561848      0.3750      human      Homo sapiens        1       9606
    taxon.Database.Name taxon.Database.ID
 1:                hg38                87
 2:                hg38                87
 3:                mm10                81
 4:                mm10                81
 5:                mm10                81
 6:                hg38                87
 7:                 rn6                86
 8:                mm10                81
 9:                mm10                81
10:                mm10                81
11:                mm10                81
12:                mm10                81
13:                mm10                81
14:                mm10                81
15:                mm10                81
16:                mm10                81
17:                mm10                81
18:                mm10                81
19:                mm10                81
20:                hg38                87
# all datasets with ontology terms for Alzheimer's disease and Parkinson's disease
# this is equivalent to using the uris parameter
get_datasets(filter = 'allCharacteristics.valueUri in (http://purl.obolibrary.org/obo/MONDO_0004975,http://purl.obolibrary.org/obo/MONDO_0005180
)')
    experiment.ShortName
 1:              GSE1556
 2:              GSE1555
 3:              GSE4757
 4:              GSE6613
 5:             GSE12685
 6:             GSE14499
 7:             GSE10908
 8:              GSE1297
 9:          E-MEXP-2280
10:             GSE20219
11:             GSE26927
12:             GSE27888
13:             GSE28146
14:             GSE29680
15:             GSE32536
16:             GSE32645
17:             GSE29317
18:             GSE15222
19:             GSE34879
20:             GSE37263
                                                                                                                                     experiment.Name
 1:                                                                                                          Control vs. APPSw mice gene expressions
 2:                                                                                         Vehicle and sAPPalpha-treated hippocampal slice cultures
 3:                                                                                                                         Rogers-3U24NS043571-01S1
 4:                                                                                                    Parkinson's disease vs. controls, whole blood
 5:                                                             Expression of mRNAs Regulating Synaptic Function and Neuroplasticity in Incipient AD
 6:                                                                          Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease
 7:                                                                           Differential gene expression in ADAM10 over-expressing transgenic mice
 8:                                                                                   Incipient Alzheimer's Disease: Microarray Correlation Analyses
 9:                                       Comprehensive mRNA expression profiling distinguishes tauopathies and identifies shared molecular pathways
10:                                                           Effects of Long-term Pioglitazone Treatment on Peripheral and Central Markers of Aging
11:                                                                                 Common neuroinflammatory pathways in neurodegenerative diseases.
12:                                                                               Comparative transcriptome analysis of APPs?-DM and APLP2-KO brains
13: Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer’s disease
14:                          Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study
15:                                              Long-term pioglitazone improves learning and attenuates pathological markers in a mouse model of AD
16:                                                                   The unique molecular signature of cortical tissue injury in Multiple Sclerosis
17:                                   Adult and neonatal astrocytes exhibit diverse gene expression profiles during exposure to beta amyloid ex vivo
18:                                                                     Genetic control of human brain transcript expression in Alzheimer’s disease.
19:                                                          Probing sporadic and familial Alzheimer?s disease using induced pluripotent stem cells.
20:                                            Genome-wide profiling of altered gene expression in the neocortex of Alzheimer's disease (gene level)
    experiment.ID
 1:            27
 2:           250
 3:           275
 4:           529
 5:           910
 6:           924
 7:           926
 8:          1565
 9:          1901
10:          1911
11:          2684
12:          2727
13:          3336
14:          3374
15:          4699
16:          5512
17:          5528
18:          5643
19:          5722
20:          5811
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      experiment.Description
 1:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   Gene expression changes in mice overexpressing amyloid precursor protein with the Swedish mutation (Tg2576; APPSw).  The gene expression levels in male 12 month-old APPSw mice (GSM26708, GSM26709) were compared to those in male nontransgenic littermate control mice (GSM26706, GSM26707).  Data were analyzed with MAS 5.0 and scaled to 2500.  See Stein, TD, Anders, NJ, DeCarli, C, Chan, SL, Mattson, MP, and Johnson JA.  Neutralization of transthyretin reverses the neuroprotective effects of secreted APP in APPSw mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci. in press.\nDate GSE1556 Last Updated: May 29 2005\nContributors:  Thor D Stein Jeffrey A Johnson\nIncludes GDS811.\n Update date: Nov 15 2004.\n Dataset description GDS811: Expression profiling of brain left hippocampi from 12 month old Tg2576 transgenics overexpressing the amyloid precursor protein with the Swedish mutation (APPSw).  APPSw linked to the early-onset Alzheimer's disease.  Tg2576 express neuroprotective genes that prevent neuronal cell loss.
 2:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   Gene expression changes induced by alpha-secretase cleaved amyloid precursor protein (sAPPalpha) in organotypic hippocampal slice cultures of male, postnatal day 15 mice (C57B6/SJL).  Hippocampal slice cultures were treated with phosphate buffered saline (GSM26700, GSM26701, GSM26702) or 1 nM sAPPalpha (GSM26703, GSM26704, GSM26705) for 24 h.  Each sample consists of total RNA isolated from 8-12 slices from 4 mice.  Data were analyzed with MAS 5.0 and scaled to 2500.  sAPPalpha induces the amyloid sequestration protein transthyretin, insulin-like growth factor 2, insulin-like growth factor binding protein 2, and other genes involved in protective pathways such as apoptosis inhibition, detoxification, and retinol transport.  See Stein, TD, Anders, NJ, DeCarli, C, Chan, SL, Mattson, MP, and Johnson JA.  Neutralization of transthyretin reverses the neuroprotective effects of secreted APP in APPSw mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci. in press.\nLast Updated (by provider): Oct 28 2005\nContributors:  Jeffrey A Johnson Thor D Stein\nIncludes GDS809.\n Update date: Nov 15 2004.\n Dataset description GDS809: Expression profiling of hippocampal slice cultures treated with 1 nM  alpha-secretase cleaved amyloid precursor protein (sAPPalpha) for 24 hours.  Hippocampi obtained from 15 day postnatal C57B6/SJL males.  Results provide insight into the neuroprotective activity of sAPPalpha.
 3:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Alzheimer's Disease (AD) is a devastating neurodegenerative disorder affecting approximately 4 million people in the U.S. alone.  AD is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain.  These pathological markers are thought to be responsible for the massive cortical neurodegeneration and concomitant loss of memory, reasoning, and often aberrant behaviors that are seen in patients with AD.  Understanding the molecular mechanisms whereby these histopathological markers develop will greatly enhance our understanding of AD development and progression.  A clearer understanding of the mechanisms underlying neurofibrillary tangle formation specifically may help to clarify the basis for dementia of AD as well as the dementias associated with other diseases that are collectively referred to as "tauopathies." To expression profile both neurons containing neurofibrillary tangles and normal neurons from the entorhinal cortex of 10 mid-stage AD cases. The gene expression profile of neurons that contain neurofibrillary tangles will differ from the expression profile of histopathologically normal neurons from the same patient and from the same brain region.  Some of these differences will be informative as to the mechanisms of tangle formation. First use laser capture microdissection to select 1000 neurons bearing neurofibrillary tangles and 1000 normal neurons from the layer 2 stellate island neurons of the entorhinal cortex of 10 mid-stage AD cases.  Second, to isolate the RNA from these captured neurons, perform double round linear amplification and hybridize the labeled cRNA to affymetrix U133A arrays.  Third, to use paired, permutational t-tests to analyze the microarray data to select tangle-specific differences in gene expression.  For the purposes of submitting this proposal, a value of 1 ug of RNA was entered due to web site constraints on values placed in that field.  However, all samples are from LCM captured cells and the actual RNA yield is likely closer to 100 pg.\nLast Updated (by provider): May 01 2006\nContributors:  Joseph Rogers
 4:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Parkinson?s disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimer?s or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD.\nLast Updated (by provider): Jan 23 2007\nContributors:  Clemens R Scherzer
 5:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            In Alzheimer’s disease (AD), early deficits in learning and memory are a consequence of synaptic modification which are likely induced by toxic beta-amyloid oligomers (oA?).  To identify molecular targets downstream of oA? binding  we prepared synaptoneurosomes from frontal cortex of control and IAD patients, and isolated mRNAs for comparison of gene expression.  This approach elevated synaptic mRNAs above the threshold necessary for expression changes to be discriminated and also reduced other cellular mRNAs.  In patients with minimal cognitive impairment (MCI) termed incipient AD (IAD) global measures of cognition declined with increasing levels of dimeric A? (dA?).  These patients also showed increased expression of neuroplasticity related genes, many encoding 3' UTR  consensus sequences that regulate local translation in the synapse.  One such gene, GluR2, displayed elevated mRNA and protein expression in IAD.  Other neurotransmitter-related genes were also upregulated.  Overexpressed genes may induce compensatory as well as negative effects on cognition and provide targets for intervention to moderate the response to dA?. \nLast Updated (by provider): Sep 09 2008\nContributors:  Ruty Mehrian Shai Ya-Hsuan Hsu Celia Williams Yongchun Wu Bryan M Spann Yi Mo Traci Sitzer Carol A McCleary Carol A Miller
 6:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/ß-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. \nLast Updated (by provider): Jan 22 2009\nContributors:  D H Geschwind B E Schroeder E Rockenstein M V Chao G Coppola A Blesch A H Nagahara J M Conner A A Chiba M H Tuszynski L Wang A Kim S Tsukada G M Shaked E Masliah D A Merrill E Koo
 7:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the ?-secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity. To assess the influence of ADAM10 on the gene expression profile in the brain we performed microarray analysis using RNA isolated from brains of five month old mice over-expressing either the ?-secretase ADAM10 or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, 355 genes were found to be differentially expressed in ADAM10 transgenic mice and 143 genes in dnADAM10 mice. A higher number of genes was found to be differentially regulated in double-transgenic mouse strains additionally expressing the human APP V717I mutant (APP[V717I]). Thus, ?-secretase cleavage of over-expressed APP[V717I] alters CNS gene expression additionally.\nLast Updated (by provider): Jan 22 2009\nContributors:  Dietrich Trümbach Wolfgang Wurst Falk Fahrenholz Kristina Endres Rolf Postina Claudia Prinzen
 8:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      For these data, we analyzed hippocampal gene expression of nine control and 22 AD subjects of varying severity on 31 separate microarrays. We then tested the correlation of each gene's expression with MiniMental Status Examination (MMSE) and neurofibrillary tangle (NFT) scores across all 31 subjects regardless of diagnosis. These tests revealed a major transcriptional response comprising thousands of genes significantly correlated with AD markers. Several hundred of these genes were also correlated with AD markers across only control and incipient AD subjects (MMSE > 20).\nLast Updated (by provider): May 29 2005\nContributors:  Kuey-Chu Chen Philip W Landfield William R Markesbery Nada M Porter James W Geddes Eric M Blalock\nIncludes GDS810.\n Update date: Nov 01 2004.\n Dataset description GDS810: Expression profiling of brain hippocampi from 22 postmortem subjects with Alzheimer's disease (AD) at various stages of severity.  7, 8, and 7 subjects diagnosed with incipient, moderate, and severe AD respectively.  Results provide insight into mechanisms underlying the early pathogenesis of AD.
 9:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 We have constructed genome wide expression profiles from snap frozen post-mortem tissue from the medial temporal lobe of patients with four neurodegenerative disorders (5 AD, 5 PSP, 5 PiD and 5 FTD patients) and 5 control subjects. All patients were matched for age, gender, ApoE-? and MAPT (tau) haplotype. From all groups a total of 790 probes were shown to be differently expressed when compared to control individuals. The results from these experiments were then used to investigate the correlations between clinical, pathological and molecular findings. From the 790 identified probes we extracted a gene set of 166 probes whose expression could discriminate between these disorders and normal ageing. This gene set can be further developed into an accurate microarray-based classification test. Furthermore, from this dataset we extracted a disease specific set of genes and identified two aging related transcription factors (FOXO1A and FOXO3A) as possible drug targets related to neurodegenerative disease. 
10:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Background: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer’s disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While some of the TZD actions are becoming clear in AD models and may mediate their reported beneficial impact in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions.  Findings: The TZD pioglitazone (PIO) was incorporated into the diet to yield a final dose of approximately 2.3 mg/kg body weight/day. PIO reduced insulin levels irrespective of age. Interestingly, a significant reduction in the Ca2+-dependent afterhyperpolarization was seen in the aged animals with no significant change in LTP maintenance or learning and memory performance. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory changes in brain and periphery were not reversed by PIO. Conclusions:  While current research efforts continue to address the underlying processes responsible for the progressive decline in cognitive function seen during aging, available medical treatments are still very limited. Our study, therefore, was aimed at elucidating potentially novel actions of TZDs in the aging brain. Using a clinically-relevant dose and delivery method, PIO had no detectable impact on several indices of brain aging and failed to alter both peripheral and central age-related increases in inflammatory signaling. \nLast Updated (by provider): May 05 2010\nContributors:  Kuey-Chu Chen Olivier Thibault Jeremiah T Phelps Nada M Porter Katie Anderson Tristano Pancani Donald A Cohen James L Searcy Eric M Blalock Jelena Popovic James C Gant Margarita Avdiushko
11:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Neurodegenerative diseases of the central nervous system are characterised by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity and inflammation are observed in most, if not all, neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data for Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, Parkinson’s disease and schizophrenia using an extensive cohort of well characterised post-mortem CNS tissues. The analysis of whole genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease specific changes, but more importantly to uncover potential common molecular pathogenic mechanisms that could be targeted for therapeutic gain. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all 6 diseases using our primary method of analysis. However, 61 dysregulated genes were shared when comparing five and four diseases. Our analysis indicates firstly the involvement of common neuronal homeostatic, survival and synaptic plasticity pathways. Secondly, we report changes to immunoregulatory and immunomodulatory pathways in all diseases. Our secondary method of analysis confirmed significant up-regulation of a number of genes in diseases presenting degeneration and showed that somatostatin was downregulated in all 6 diseases. The latter is supportive of a general role for neuroinflammation in the pathogenesis and/or response to neurodegeneration. Unravelling the detailed nature of the molecular changes regulating inflammation in the CNS is key to the development of novel therapeutic approaches for these chronic conditions.\nLast Updated (by provider): Jan 29 2011\nContributors:  Andrea Schmitt Shama Fernando Isidro Ferrer Tim P Bonnert Edna Grünblatt Peter J Gebicke-Haerter David T Dexter Miklos Palkovits Hans Kretzschmar Danielle Seilhean Richard Reynolds Pascal F Durrenberger N B Oumesmar Thomas Arzberger Peter Falkai Samira N Kashefi
12:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Despite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and of its proteolytic fragments are still poorly understood. The secreted APPs? ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The ?-secretase generated APP intracellular domain, AICD, functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. Previously, we have generated APPs? knockin (KI) mice expressing solely the secreted ectodomain APPs?. Here, we generated double mutants (APPs?-DM) by crossing APPs?-KI mice onto an APLP2-deficient background and show that APPs? rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPs?-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP. To gain further mechanistic insight into which domains/proteolytic fragments are crucial for hippocampal APP/APLP2 mediated functions, we performed a DNA microarray transcriptome profiling of prefrontal cortex and hippocampus of adult APLP2-KO (APLP2-/-) and APPs?-DM mice (APP?/?APLP2-/- mice).Interestingly, this analysis failed to reveal major genotype-related transcriptional differences. Expression differences between cortex and hippocampus were, however, readily detectable.\nLast Updated (by provider): May 10 2011\nContributors:  Benedikt Brors Ulrike C Müller Mikhail Filippov Dorothee Aydin Sascha Weyer Norbert Gretz
13:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      Alzheimer's disease (AD) is a devastating neurodegenerative disorder that threatens to reach epidemic proportions as our population ages. Although much research has examined molecular pathways associated with AD, relatively few studies have focused on critical early stages. Our prior microarray study correlated gene expression in human hippocampus with AD markers. Results suggested a new model of early-stage AD in which pathology spreads along myelinated axons, orchestrated by upregulated transcription and epigenetic factors related to growth and tumor suppression (Blalock et al., 2004). However, the microarray analyses were performed on RNA from fresh frozen hippocampal tissue blocks containing both gray and white matter, potentially obscuring region-specific cha