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: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
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:Genome-wide prefrontal cortex and cerebellum DNA methylation profiles of younger and older adult humans, captive chimpanzees, and captive rhesus macaques
Project description:The depressive-like behavior in animals is usually assessed by standardized behavioral tests such as the forced swimming test. However, the findings of these tests may be affected by individual variability among animals, which may hinder the discovery of genes responsible for depression. Few reports have showed the influence of individual variability in identifying the genes associated with depressive-like behavior. In this study, we measured the immobility ratio (% immobility in 5 min) in the forced swimming test in 106 male Wistar rats. According to the distribution of individual immobility ratio, the rats were divided into three groups: the control group with immobility ratio -1 to +1 standard deviation (SD) from the mean, the depressive group with immobility ratio +1 to +2 SD above the mean, and the anti-depressive group with immobility ratio -1 to -2 SD below the mean. Microarray analysis was used to identify the genes differentially expressed by depressive group rats in the prefrontal cortex and cerebellum. The differentially expressed genes in both brain regions of the depressive group were Alas2, Gh1, Hba-a2, Hbb, Hbb-b1, Hbe2, LOC689064, Mrps10, Mybpc, Olf6415, and Pfkb1. Ingenuity pathway analysis identified Gh1 as a hub gene in the networks of the differentially expressed genes in both brain regions. This study indicates that inherent differences in depressive-like behavior may be related to the Gh1 expression in the cerebellum and prefrontal cortex. We measured the immobility ratio of 106 normal rats using the forced swimming test and statistically analysis. We selected the rats exhibitting depressive-like behavior or average in the 106 rats. Total RNA was prepareted from the cerebellum and prefrontal cortex. An equal amount of RNA from 4 rats in each group was pooled and used for microarray analysis.
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: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:Fresh frozen post mortem prefrontal cortex tissue (Brodman area 46) was obtained from 44 individuals varying in age from 0 to 49 years. RNA was extracted from these samples and hybridized to HG133plus2.0 GeneChips. The data was used to examine patterns of gene expression over the course of human postnatal developmental and ageing. PMI - postmortem interval, DLPFC - dorsolateral prefrontal cortex Experiment Overall Design: The dataset consists of 44 individuals varying in age from 0 to 49 years
Project description:To understand the roles of molecules in functional differentiation among adult human tissues, we performed a systematic survey of mRNA, protein, and protein phosphorylation as well as miRNA expression, in three tissues: cerebellum, prefrontal cortex and liver. We found that tissues were clearly distinct from one another at all levels. Furthermore, our results showed that miRNA differently expressed between tissues have significant, but modest effect on expression of mRNA and somewhat stronger effect on expression of proteins among the tissues. Notably, miRNA preferentially targeted gene regulators, transcription factors and kinases, in all three tissues studied. Following this path, we found that miRNA effect was further amplified through expression changes of target transcription factors and kinases, leading to further changes in their targets’ expression and phosphorylation levels. Importantly, miRNA regulation leads to reduced, rather than increased gene expression variation among individuals between two brain regions. These observations uncover the complexity of miRNA regulatory interactions and are compatible with suggested role of miRNA in gene expression canalization. Adult human post-mortem tissue samples: cerebellum, prefrontal cortex and liver, were collected. Each tissue contains three individuals totalling 9 samples in this datasets. RNA extracted from these dissected tissue was hybridized to Agilent Human miRNA Microarray.