Project description:Schizophrenia-associated anomalies in gene expression in postmortem brain are caused by a combination of genetic and environmental influences. Given the small effect size of common variants it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. However, at the gene level we will see more impact from common environmental risk factors mediated by influential epigenomic modifiers. In this study we examine changes in cortical gene expression to identify regulatory interactions and networks associated with the disorder. Gene expression analysis in post-mortem prefrontal dorsolateral cortex (BA 46) (n=74 matched pairs of schizophrenia, schizoaffective and control samples) was performed using Illumina HT12 gene expression microarrays. Significant gene interaction networks were identified for differentially expressed genes in pathways of neurodevelopmental and oligodendrocyte function.
Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This is analysis of 18 RNA samples, including 9 technical replicates. Two strains of rats selected for extreme levels of ethanol preference (low preferring WLP and high preferring WHP) were compared. Three brain areas (nucleus accumbens, prefrontal medial cortex and hippocampus) were studied. For each brain area, 6 RNA samples (including 3 technical replicates) were analyzed. Each RNA sample consist of of equal amounts of total RNA from 3 male rats. Comparisons: Nucleus accumbens of WHP vs. Nucleus accumbens of WLP; Prefrontal medial cortex of WHP vs. Prefrontal medial cortex of WLP; Hippocampus of WHP vs. Hippocampus of WLP. 3 biological replicates in each comparison.
Project description:Analysis of transcriptiomic alternations related with alcohol use disorders (AUDs). The hypothesis is that chronic alcohol consumption might alter genome-wide gene expression patterns. The results suggest that differential gene expression in the prefrontal cortex is implicated in neuroadaptations to alcohol. Total RNAs were extracted from postmortem prefrontal cortex tissues from 23 AUD cases and 23 matched controls. Both AUD cases and matched controls were assessed with DSM-IV.
Project description:This SuperSeries is composed of the following subset Series:; GSE5388: Adult postmortem brain tissue (dorsolateral prefrontal cortex) in subjects with bipolar disorder; GSE5389: Adult postmortem brain tissue (ortibtofrontal cortex) in subjects with bipolar disorder; Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex and orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls. Experiment Overall Design: Refer to individual Series
Project description:Purpose: The goal of this study to examine mRNA transcriptomic changes in reward-related brain regions of subjects with alcohol use disorder. Methods: Total RNAs were extracted from postmortem prefrontal cortex of 12 AUD and 12 control subjects. rRNA depletion RNA sequencing was performed and the sequence reads were processed using the bulk RNA-seq processing pipeline Pipeliner workflow (Federico et al. Front Genet 2019; 10, 614). AUD-associated mRNA transcriptomic changes were analyzed by the Limma-Voom method. Results: Differentially expressed mRNAs (absolute FC>2.0 & P<0.05) were identified in postmortem prefrontal cortex of subjects with alcohol use disorder (AUD). Chronic alcohol consumption may alter mRNA transcriptome profiles in reward-related brain regions, resulting in alcohol-induced neuroadaptations.
Project description:A total of 36 postmortem brain samples (23 suicide completers, 13 control sudden death) were collected. We evaluated the proteome profile in the prefrontal cortex (Brodmann area 9, 10) with TMT-based quantification using LC-MS/MS. Several bioinformatics tools were used to elucidate biological mechanisms related to suicide. Subgroup analysis was conducted to find common differentially expressed proteins (DEPs) among various clinically different groups. Among the 9801 proteins identified in our dataset, 295 proteins were differentially expressed between suicide completers and sudden death subjects. Various bioinformatics analysis revealed that suicide completion is predominately enriched in synaptic functions and synaptogenesis especially in endocannabinoid and GABA signaling pathway. Our finding presents the largest protein pools related to suicide completion, and suggests that newly emerging neurotransmitter systems such as endocannabinoid system and synaptogenesis processes may have an impact upon the biological cascade leading to suicide.
Project description:The human brain has changed dramatically since humans diverged from our closest living relatives, chimpanzees and the other great apes. However, the genetic and developmental programs underlying this divergence are not fully understood. Here, we generate single-nucleus RNA-seq data of human, chimpanzee and macaque adult prefrontal cortex. Spatial information is obtained by isolating nuclei from sequential sections sliced from basal to apical positions. By comparing transcriptome of different cell types in the three species, we map human-specific expression in adult prefrontal cortex. By comparing to single cell RNA-seq data of cerebral organoids of the same species, we find developmental differences that persist into adulthood, as well as cell state-specific changes that occur exclusively in the adult brain.
Project description:Analysis of methylomic alternations related with alcohol use disorders (AUD). The hypothesis is that chronic alcohol consumption might alter genome-wide DNA methylation patterns. The results suggest that differential DNA methylation might be invovled in neuradaptations to alcohol. Genomic DNA was extraced from postmortem prefrontal cortex tissues of 23 AUD cases and 23 matched controls. Both AUD cases and matched controls are assessed with DSM-IV