Transcription profiling of human cerebellum from schizophrenia patients and normal subjects
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
DISEASE(S): schizophrenia
SUBMITTER: Elizabeth Salomon
PROVIDER: E-GEOD-4036 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Malfunction of multiple regions in distributed brain circuits has been suggested to underlie the diversity of symptoms and cognitive impairments in schizophrenia. The cerebellum, as part of this circuit, may contribute to these symptoms for this reason we undertook a proteomic profile of this region. Here, we design a quantitative exploratory proteomic analysis in pooled grey matter of the cerebellum from schizophrenia and control individuals with the aim of discovering consistently altered biomarker proteins in schizophrenia.
2020-06-22 | PXD008216 | Pride
Project description:Despite the growing importance of the cortico-cerebellar-thalamo-cortical circuit in schizophrenia, limited information is available regarding altered molecular networks in cerebellum. To identify altered protein networks, we conducted proteomic analysis of grey matter of postmortem cerebellar cortex in chronic schizophrenia subjects (n=12) and healthy individuals (n=14) followed by an extensive bioinformatic analysis. Two double-hit postnatal stress murine models for SZ were used to validate the most robust candidates.
2021-12-30 | PXD024937 | Pride
Project description:Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular etiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, many residing in the vicinity of genes previously implicated in schizophrenia including NCAM1, SYNPO, GBP4, PRDM9, GADD45B and DISC1. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with etiological variation in complex disease.
2016-11-10 | GSE89702 | GEO
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. Prefrontal cortex (PFC) and cerebellum samples were obtained from 46 brains archived in the London Brain Bank for Neurodegenerative Disorders (LBBND). Of these 22 were schizophrenia cases, ands of the cases 12 were male.
2014-09-18 | E-GEOD-61431 | biostudies-arrayexpress
Project description:Schizophrenia is associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction is manifest as cognitive deficits that appear to arise from disturbances in gamma frequency oscillations. These oscillations are generated in DLPFC layer 3 via reciprocal connections between pyramidal cells and parvalbumin (PV)-containing interneurons. The density of cortical PV neurons is not altered in schizophrenia, but expression levels of several transcripts involved in PV cell function, including PV, are lower in the disease.
2018-07-01 | GSE93577 | GEO
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.
2014-09-13 | E-GEOD-61380 | biostudies-arrayexpress
Project description:The purpose of the study was to identify altered molecular networks in the prefrontal cortex of schizophrenia patients by comparing protein expression levels in autopsied brains of patients (n=10) and controls (n=10), using aquantitative proteomics.
2018-01-01 | PXD008227 | JPOST Repository
Project description: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. Keywords: other
2006-01-13 | GSE4036 | GEO
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects.
2014-09-18 | GSE61431 | GEO
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects.
2014-09-13 | GSE61380 | GEO