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Gene co-expression networks in human brain predict chromatin modifications in alcohol abusers

ABSTRACT: A novel systems approach was applied to transcriptome profiling that included the traditional analysis of differentially expressed genes, gene co-expression networks, cell type - specific transcriptomes and a wide range of gene annotations. By integrating our data with previous findings, we generated the first systems hypothesis of human alcoholism that integrates epigenetic regulation of gene expression with structural and functional alterations in alcoholic brain.

ORGANISM(S): Homo sapiens

PROVIDER: GSE29555 | GEO | 2011/07/12

SECONDARY ACCESSION(S): PRJNA141323

REPOSITORIES: GEO

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Gene co-expression networks in human brain predict chromatin modifications in alcohol abusers

Project description:A novel systems approach was applied to transcriptome profiling that included the traditional analysis of differentially expressed genes, gene co-expression networks, cell type - specific transcriptomes and a wide range of gene annotations. By integrating our data with previous findings, we generated the first systems hypothesis of human alcoholism that integrates epigenetic regulation of gene expression with structural and functional alterations in alcoholic brain. Total RNA was extracted from human post-mortem brain and gene expression profiles were compared between alcoholics and matched controls.

2011-07-12 | E-GEOD-29555 | biostudies-arrayexpress

THE EFFECTS OF ALCOHOLISM ON THE HUMAN BASOLATERAL AMYGDALA

Project description:Alcohol affects gene expression in several brain regions. The amygdala is a key structure in the brainâs emotional system and in recent years the crucial importance of the amygdala in drug-seeking and relapse has been increasingly recognized. In this study gene expression screening was used to identify genes involved in alcoholism in the human basolateral amygdala. The results show that alcoholism affects a broad range of genes and many systems including genes involved in synaptic transmission, neurotransmitter transport, structural plasticity, metabolism, energy production, transcription and RNA processing and the circadian cycle. In particular, genes involved in the glutamate system were affected in the alcoholic patients. In the amygdala the glutamate system is involved in the acquisition, consolidation, expression and extinction of associative learning, which is a vital part of addiction, and in alcohol abusers it is associated with withdrawal anxiety and neurodegeneration. Downregulation of the excitatory amino acid transporters GLAST, GLT-1 and the AMPA glutamate receptor 2 (GluR2) revealed by the microarray were confirmed by Western blots. The decreased expression of GLAST, GLT-1 and GluR2 in the alcoholic patients may increase glutamate tone and activity in the basolateral amygdala and this may contribute to neurodegeneration as well as the expression of associative memories and anxiety which underlie continued drug-seeking and chronic relapse. Two-condition experiment, alcoholics vs controls. Biological replicates: 6 alcoholics 6 controls, one replicate per array.

2010-05-22 | E-GEOD-18212 | biostudies-arrayexpress

Transcriptional Response to Alcohol Exposure in Drosophila melanogaster

Project description:The National Institute on Alcohol Abuse and Alcoholism has estimated that approximately 14 million people in the United States suffer from alcoholism. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Whereas environmental factors, such as stress and social experience, contribute to individual variation in sensitivity to chronic alcohol consumption, genetic factors have also been implicated. However, genetic polymorphisms that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of olfactory sensitivity and, concomitant with development of tolerance, altered transcription of enzymes associated with fatty acid biosynthesis. Our results identify key enzymes in conserved metabolic pathways that may contribute to human alcohol sensitivity. Keywords: Drosophila, model system, alcohol sensitivity, tolerance

2006-07-27 | GSE5382 | GEO

THE EFFECTS OF ALCOHOLISM ON THE HUMAN BASOLATERAL AMYGDALA

Project description:Alcohol affects gene expression in several brain regions. The amygdala is a key structure in the brain’s emotional system and in recent years the crucial importance of the amygdala in drug-seeking and relapse has been increasingly recognized. In this study gene expression screening was used to identify genes involved in alcoholism in the human basolateral amygdala. The results show that alcoholism affects a broad range of genes and many systems including genes involved in synaptic transmission, neurotransmitter transport, structural plasticity, metabolism, energy production, transcription and RNA processing and the circadian cycle. In particular, genes involved in the glutamate system were affected in the alcoholic patients. In the amygdala the glutamate system is involved in the acquisition, consolidation, expression and extinction of associative learning, which is a vital part of addiction, and in alcohol abusers it is associated with withdrawal anxiety and neurodegeneration. Downregulation of the excitatory amino acid transporters GLAST, GLT-1 and the AMPA glutamate receptor 2 (GluR2) revealed by the microarray were confirmed by Western blots. The decreased expression of GLAST, GLT-1 and GluR2 in the alcoholic patients may increase glutamate tone and activity in the basolateral amygdala and this may contribute to neurodegeneration as well as the expression of associative memories and anxiety which underlie continued drug-seeking and chronic relapse.

2009-09-24 | GSE18212 | GEO

Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding Canonical miRNAs: A Pilot Biomarker Study of Using isomiR-ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD

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2005-11-19 | GSE3632 | GEO

Post-alcoholism and post-hepatitis C cirrhosis

Project description:The aim of this study is to compare post-hepatitis C virus (HCV) and post-alcoholism cirrhosis gene expression profiling. By transcriptome analysis with a cDNA array virtually covering every transcript in liver, we compared transcript levels in alcoholic- , HCV-cirrhosis and control liver. A stringent selection identified a list of 70 transcripts which completely separated the 3 groups of patients (7 HCV-cirrhosis, 7 alcoholic cirrhosis and 8 control livers). In contrast, in an hepatocellular carcinoma (HCC) context, comparison of 10 HCV-cirrhosis, 10 alcoholic cirrhosis and the 8 control livers failed to identify such transcripts. We report that dysregulations at the transcriptional level do exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC. Keywords: etiology-dependent and HCC-dependent analysis

2008-02-01 | GSE10356 | GEO

Transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of alcohol-preferring and nonpreferring rats

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 study was supported through funding from the following grants: Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants “Iuventus Plus” (IP2011 030371) and N N519 657940.

2015-01-17 | GSE65064 | GEO

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A chemoproteomics approach to profile phospholipase D-derived phosphatidyl alcohol interactions

Project description:Alcohol consumption leads to formation of phosphatidylethanol (PEth) via the transphosphatidylation activity of phospholipase D (PLD) enzymes. Though this non-natural phospholipid routinely serves as a biomarker of chronic alcoholism, its pathophysiological roles remain unknown. We use a minimalist diazirene alkyne alcohol as an ethanol surrogate to generate clickable, photoaffinity lipid reporters of PEth localization and lipid–protein interactions via PLD-mediated transphosphatidylation. Using click chemistry tagging, enrichment, and proteomics analysis, we identified the single-pass transmembrane protein basigin/CD147 as a high-confidence interaction partner of this photoaffinity lipid reporter. Here we perform in-cell photocrosslinking, followed by anti-FLAG affinity enrichment of FLAG-tagged basigin, to map the crosslinking sites and determine that the PAL lipid crosslinks to a C-terminal peptide of basigin-FLAG. This study provides a view of the molecular interactions of phosphatidyl alcohols and points to future work to connect such interactions to potential pathophysiological roles of PEth.

2024-01-04 | PXD029749 | Pride

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