Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in the NAc and PFC [miRNA]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA680295 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n=35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc=6; PFC=3) and miRNA (NAc=3; PFC=2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc=6; PFC=4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA=37, miRNA=9; PFC: mRNA=17, miRNA=16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
2020-11-24 | GSE161997 | GEO
Project description:Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n=35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc=6; PFC=3) and miRNA (NAc=3; PFC=2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc=6; PFC=4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA=37, miRNA=9; PFC: mRNA=17, miRNA=16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
2020-11-24 | GSE161986 | GEO
Project description:Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in the NAc and PFC
| PRJNA680289 | ENA
Project description:Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in the NAc and PFC [mRNA]
| PRJNA680299 | ENA
Project description: Not available
| S-EPMC7745987 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-24 | GSE161999 | GEO
Project description:Drugs of abuse including nicotine and alcohol elicit their effect by stimulating the mesocorticolimbic dopaminergic system. There is a high incidence of nicotine dependence in alcoholics. To date only limited data is available on the molecular mechanism underlying the action of alcohol and nicotine in the human brain. This study utilised gene expression screening to identify genes sensitive to chronic alcohol abuse within the ventral tegmental area of the human brain. Keywords: gene expression, brain, alcohol abuse, human, ventral tegmental area
2007-09-21 | GSE9058 | GEO
Project description:This project will chart with high-resolution the genetic pathways that give rise to defined clinical phenotypes related to cocaine addiction. We will utilize the power of the hybrid mouse diversity panel (HMDP), combined with high quality behavioral phenotyping and massive-scale RNA sequencing, to trace the interconnections from DNA to RNA to clinical trait and provide layered information on the mechanisms of cocaine abuse. The HMDP consists of 100 inbred and recombinant inbred strains and has a wide array of meiotic breakpoints. The panel has been densely genotyped with more than 200,000 single nucleotide polymorphisms (SNPs), allowing very fine mapping of quantitative trait loci (QTLs). Further, the HMDP is genetically stable and renewable and can be assayed for multiple phenotypes, yielding cumulative biological information. We will expand our previous HMDP-based studies of cocaine abuse-related traits by adding massive-scale RNA sequencing (RNA-Seq), in order to detail the genetic control of the pathways to addiction.
2021-11-02 | GSE186981 | GEO
Project description:Background: The incidence of alcohol and tobacco co-abuse is as high as 80%. The molecular mechanism underlying this comorbidity is virtually unknown but interactions between these drugs have important implications for the development of, and recovery from drug dependence. Methods: We investigated the effects of chronic tobacco and alcohol abuse and the interaction of the two behaviours on global gene expression in the human nucleus accumbens using cDNA microarrays and 20 alcoholic and control cases, with and without smoking comorbidity. Changes in gene expression were established by two-way ANOVA. Unsupervised hierarchical clustering was utilized to probe the strength of the data sets. Results: Subjecting the data sets derived from microarray gene expression screening to unsupervised hierarchical clustering tied the cases into distinct groups. When considering all alcohol-responsive genes, alcoholics were separated from non alcoholics with the exception of one control case. All smokers were distinguished from non smokers based on similarity in expression of smoking-sensitive genes. In the nucleus accumbens, alcohol-responsive genes were associated with transcription, lipid metabolism and signalling. Smoking-sensitive genes were predominantly assigned to functional groups concerned with RNA processing and the endoplasmic reticulum. Both drugs influenced the expression of genes involved in matrix remodelling, proliferation and cell morphogenesis. Additionally, a gene set encoding proteins involved in the canonical pathway ‘regulation of the actin cytoskeleton’ was induced in response to alcohol and tobacco co-abuse and included. Conclusions: The region-specific modulation of alcohol-sensitive gene expression by smoking may have important consequences for alcohol-induced aberrations within the mesolimbic dopaminergic system. The data set contained individual RNA samples extracted from the nucleus accumbens from 5 non smoking non drinking control case, 5 non smoking alcoholics, 5 non drinking smokers, and 5 smoking alcoholics. An aliquot if each sample was combined to generate a reference pool. Each sample was amplified individually and labelled with Cy3 in the process, the reference samples was amplified and labelled with Cy5. Each sample was hybridised competitively against the reference sample to 1 array.
2010-07-01 | E-GEOD-20568 | biostudies-arrayexpress
Project description:The mechanisms of aciotn of modafinil continue to be poorly characterised and its potential for abuse remains controverted. The aim of this study was to further elucidate the mechanism of action of modafinil, through a potential behavioural and molecular association in the mouse. A conditioned place preference (CPP) paradigm was implemented to investigate the rewarding properties of modafinil. Whole genome expression and qRT-PCR analysis were performed on the ventral tegmental area (VTA), nucleus accumbens (NAC) and prefrontal cortex (PFC) of modafinil-treated and control animals. We used microarrays to detail gene expression in the ventral tegmental area (VTA), nucleaus accumbens (NAC) and prefrontal cortex (PFC) of the vehicle and modafinil treated animals to profile whole genome expression in the selected brain regions.
2015-10-15 | GSE74010 | GEO