Gene expression in human post-mortem brain samples from schizophrenic subjects and matched controls
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE27356 | GEO | 2011/02/17
SECONDARY ACCESSION(S): PRJNA137043
REPOSITORIES: GEO
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Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Gene expression patterns from the pefrontal cortical region (Brodmann Area 46) of subjects with schizophrenia and age- and sex-match control subjects was analyzed. The prefrontal cortex was chosen since it is a primary brain region implicated in the pathophysiological of schizophrenia. Furthermore, this region was used in our previous proteomics studies, allowing for the direct comparison of changes in protein levels to gene expression results. 16 schizophrenic subjects were studied, consisting of 8 subjects with duration of illness (DOI) < 5 years and 8 subjects with DOI > 22 years. 16 age- and sex-matched controls were also studied. Gene expression profiles were analyzed from individual subjects; a total of 32 samples were hybridized to the custom designed CFG GLYCOv2 glycogene array.
2011-02-17 | E-GEOD-27356 | biostudies-arrayexpress
Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Extension of previous studies investigating Glyco-Gene Expression in Schizophrenia (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27356 ). From previous analyses, a group of 9 genes associated with the biosynthesis of glycosphingolipids were identified as altered in subjects with schizophrenia, with most differences detected in subjects with short DOI and not in chronic illness. The enzyme expression changes are of particular interest as they are important to the synthesis of cerebrosides and sulfatides, which are enriched in membranes making up myelin. There are known deficits in myelin and white matter in schizophrenia so changes in these enzymes may represent a mechanism accounting for these deficits. Furthermore, clusters of co-regulated genes were identified using new software for weighted gene co-networks. This may represent the first molecular definition of different subtypes of schizophrenia, a very heterogeneous psychiatric disorder.
2011-03-02 | GSE27601 | GEO
Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Extension of previous studies investigating Glyco-Gene Expression in Schizophrenia (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27356 ). From previous analyses, a group of 9 genes associated with the biosynthesis of glycosphingolipids were identified as altered in subjects with schizophrenia, with most differences detected in subjects with short DOI and not in chronic illness. The enzyme expression changes are of particular interest as they are important to the synthesis of cerebrosides and sulfatides, which are enriched in membranes making up myelin. There are known deficits in myelin and white matter in schizophrenia so changes in these enzymes may represent a mechanism accounting for these deficits. Furthermore, clusters of co-regulated genes were identified using new software for weighted gene co-networks. This may represent the first molecular definition of different subtypes of schizophrenia, a very heterogeneous psychiatric disorder. For this follow up study, microarray analyses experiments were performed on an additional cohort of subjects with schizophrenia in order to, 1) Assess how this group of glycosphingolipid-related genes is altered in disease and control states, and 2) Further determine if co-regulated genes will cluster in the new cohort, which will consist of subjects with a range of durations of illness. For these studies, 32 human samples (16 control and 16 Schizophrenic) were labeled and hybridized to 26 GLYCOv2 arrays
2011-03-02 | E-GEOD-27601 | biostudies-arrayexpress
Project description:Introduction: Parkinson's disease (PD) is characterized by bradykinesia, tremor, and rigidity; in addition, postural instability sets in as the disease progresses. Non-motor symptoms of the disease include cognitive, behavioral, and neuropsychiatric changes, sensory and sleep disturbances that may precede the motor symptoms of the disease itself. The peculiar pathological features of PD are decreased dopaminergic neurons and dopamine levels in the substantia nigra pars compacta and pontine locus ceruleus. The study of the transcriptome plays a major role in the identification of genes and gene regulatory mechanisms in multifactorial neurodegenerative diseases such as Parkinson's disease itself. Therefore, we proposed to study the transcriptome directly in the midbrain containing the "Substantia nigra.The study was performed in 8 subjects with PD and 6 normal control subjects, using next-generation sequencing (NGS) technologies. Results: With the use of an ad hoc bioinformatics pipeline, gene expression profiles in the different PD subjects were obtained and compared to those of controls. In detail, the results obtained from the data analysis indicated 92 differentially expressed genes (FDR-adjusted p value ≤0.05 and fold-change less than -1.5 or greater than +1.5) of which 33 genes were up-regulated while 59 were down-regulated. Conclusions: Functional analysis of the differentially expressed genes revealed several genes involved in different canonical pathways indicating their likely significant role in Parkinson's disease.
2024-01-03 | E-MTAB-13295 | biostudies-arrayexpress
Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Our goal is to elucidate mechanisms by which regulated expression of proteoglycans and glycosylation-related genes contribute to neurodegenerative diseases involving the striatum. A number of studies have demonstrated that neural proteoglycans are involved structural organization of the striatum and formation of dopaminergic connections to and from the striatum. Several proteoglycans are also associated with neuronal regeneration and some have been shown to be components of filamentous inclusions found in neurodegenerative disorders. In addition, the localization and proper function of dopamine receptors, which are predominantly expressed in the striatum, are governed by N-linked glycosylation events. Huntingtonís Disease (HD), a progressive neurodegenerative disorder, results in selective degeneration of the striatum. This is caused by a mutation in the protein, huntingtin, however, the mechanisms responsible for neuronal degeneration remain unknown. Similar to the brains of HD patients, HD transgenic mice exhibit huntingtin protein aggregation and nuclear inclusions, selective degeneration of dopamine neurons in the striatum and dopamine receptor dysfunction. In this study, the gene expression patterns of HD transgenic mice were analyzed. Four groups, pre-symptomatic HD mice (6 weeks old), WT control (6 weeks), post symptomatic HD (16 weeks), and WT control (16 weeks), were hybridized and analyzed using the GLYCOv2 array. Each group was hybridized in triplicate.
2011-03-02 | E-GEOD-27588 | biostudies-arrayexpress
Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Our goal is to elucidate mechanisms by which regulated expression of proteoglycans and glycosylation-related genes contribute to neurodegenerative diseases involving the striatum. A number of studies have demonstrated that neural proteoglycans are involved structural organization of the striatum and formation of dopaminergic connections to and from the striatum. Several proteoglycans are also associated with neuronal regeneration and some have been shown to be components of filamentous inclusions found in neurodegenerative disorders. In addition, the localization and proper function of dopamine receptors, which are predominantly expressed in the striatum, are governed by N-linked glycosylation events. Huntingtonís Disease (HD), a progressive neurodegenerative disorder, results in selective degeneration of the striatum. This is caused by a mutation in the protein, huntingtin, however, the mechanisms responsible for neuronal degeneration remain unknown. Similar to the brains of HD patients, HD transgenic mice exhibit huntingtin protein aggregation and nuclear inclusions, selective degeneration of dopamine neurons in the striatum and dopamine receptor dysfunction.
2011-03-02 | GSE27588 | GEO
Project description:Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients.
2009-08-13 | GSE17612 | GEO
Project description:Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences. Experimental design: Two groups of male control subjects and female control subjects were selected that had no history of psychiatric disorder. Each subject was analyzed by microarray in 3 brain regions: AnCg (anterior cingulate cortex), DLPFC (dorsalateral prefrontal cortex), and CB (cerebellum). Total RNA aliquots for some subjects were analyzed at either 1 site, 2 sites, or 3 sites (UM , University of Michigan); UCD (University of California, Davis); or UCI (University of California, Irvine). The data was analyzed by looking at each Male vs Female comparison separately at each site by a t-test for gender differences. Thus for one brain region, a Male vs Female comparison was run at 3 sites, and the overlapping significant genes from the three comparisons were reported. We appreciate the assistance of Richard Stein, Ph.D. and Preston Cartagena, Psy.D. for their contributions to postmortem clinical characterization of subjects. We acknowledge Kathleen Burke as well as Jacque Berndt and the investigators and medical examiners at the Orange County Coroners Office for procurement of brain tissue. We also appreciate the technical contributions of Kevin Overman, Sharon Burke, and Phong Nguyen. F. Warren Lovell, M.D, performed a neuropathological evaluation of the postmortem brains. Tissue specimens were processed and stored at the Human Brain and Spinal Fluid Resource Center, Veteran's Medical Center, Los Angeles under the direction of Wallace W. Tourtellotte, M.D., Ph.D. This project is supported by the NIMH Conte Center Grant P50 MH60398, Pritzker Neuropsychiatric Disorders Research Consortium, William Lion Penzner Foundation (UCI), Della Martin Foundation (UCI), NIMH Grant #MH54844 (EGJ), W.M. Keck Foundation (EGJ), and the NIMH Program Project MH42251 (SJW and HA). The authors are members of of a Conte Center supported by the NIMH and the Pritzker Neuropsychiatric Disorders Research Consortium, which is supported by the Pritzker Neuropsychiatric Disorders Research Fund L.L.C. A shared intellectual property agreement exists between this philanthropic fund and the University of Michigan, the University of California, and Stanford University to encourage the development of appropriate findings for research and clinical applications. Keywords: other
2005-01-28 | GSE2164 | GEO
Project description: Not available
| S-EPMC2776935 | biostudies-other
Project description:Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development Schizophrenia is a highly debilitating psychiatric disorder which is known to have heritable genetic and environmental components. To gain some insight into the mechanisms underpinning both positive and negative symptoms of the disease, we determined the genome wide expression of mRNA transcripts in post-mortem tissue from the superior temporal cortex (Brodmann Area 22, BA22) in schizophrenic and control patients. The BA22 region is known to mediate the positive pathophysiology of schizophrenia; we compared this to the anterior prefrontal cortex (BA10) from the same subjects, which is known to mediate negative symptoms. Following adjustments for confounding clinical, sample and experimental sources of variation, we carried out gene set enrichment analysis in each region using pathway data. We identified an over-representation of genes involved in cytoskeletal remodelling, neurodevelopment, cell adhesion, cellular signalling, neurotransmission and autophagy. Collectively our analysis indicates a disruption of processes underpinning synaptic plasticity in both regions. Region-specific changes support the dysregulation of distinct pathways in the BA10 and BA22 regions. This may highlight new therapeutic opportunities to treat both negative and positive symptoms of the disease.
2011-12-31 | GSE21935 | GEO