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A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure

Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the...

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Autores principales: Enoch, Mary-Anne, Baghal, Basel, Yuan, Qiaoping, Goldman, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661725/
https://www.ncbi.nlm.nih.gov/pubmed/23717525
http://dx.doi.org/10.1371/journal.pone.0064014
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author Enoch, Mary-Anne
Baghal, Basel
Yuan, Qiaoping
Goldman, David
author_facet Enoch, Mary-Anne
Baghal, Basel
Yuan, Qiaoping
Goldman, David
author_sort Enoch, Mary-Anne
collection PubMed
description Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABA(A) gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from postmortem samples from nine adults. A factor analysis was performed on global expression of 21 GABAergic pathway genes. Factor specificity for response to chronic alcohol/cocaine exposure was subsequently determined from the analysis of RNA-Seq data from postmortem hippocampus of eight alcoholics, eight cocaine addicts and eight controls. Six gene expression factors were identified. Most genes loaded (≥0.5) onto one factor; six genes loaded onto two. The largest factor (0.30 variance) included the chromosome 5 gene cluster that encodes the most common GABA(A) receptor, α(1)β(2)γ(2), and genes encoding the α(3)β(3)γ(2) receptor. Genes within this factor were largely unresponsive to chronic alcohol/cocaine exposure. In contrast, the chromosome 4 gene cluster factor (0.14 variance) encoding the α(2)β(1)γ(1) receptor was influenced by chronic alcohol/cocaine exposure. Two other factors (0.17 and 0.06 variance) showed expression changes in alcoholics/cocaine addicts; these factors included genes involved in GABA synthesis and synaptic transport. Finally there were two factors that included genes with exceptionally low (0.10 variance) and high (0.09 variance) expression in the cerebellum; the former factor was unaffected by alcohol/cocaine exposure. This study has shown that there appears to be specificity of GABAergic gene groups, defined by covariation in expression, for response to chronic alcohol/cocaine exposure. These findings might have implications for combating stress-related craving and relapse.
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spelling pubmed-36617252013-05-28 A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure Enoch, Mary-Anne Baghal, Basel Yuan, Qiaoping Goldman, David PLoS One Research Article Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABA(A) gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from postmortem samples from nine adults. A factor analysis was performed on global expression of 21 GABAergic pathway genes. Factor specificity for response to chronic alcohol/cocaine exposure was subsequently determined from the analysis of RNA-Seq data from postmortem hippocampus of eight alcoholics, eight cocaine addicts and eight controls. Six gene expression factors were identified. Most genes loaded (≥0.5) onto one factor; six genes loaded onto two. The largest factor (0.30 variance) included the chromosome 5 gene cluster that encodes the most common GABA(A) receptor, α(1)β(2)γ(2), and genes encoding the α(3)β(3)γ(2) receptor. Genes within this factor were largely unresponsive to chronic alcohol/cocaine exposure. In contrast, the chromosome 4 gene cluster factor (0.14 variance) encoding the α(2)β(1)γ(1) receptor was influenced by chronic alcohol/cocaine exposure. Two other factors (0.17 and 0.06 variance) showed expression changes in alcoholics/cocaine addicts; these factors included genes involved in GABA synthesis and synaptic transport. Finally there were two factors that included genes with exceptionally low (0.10 variance) and high (0.09 variance) expression in the cerebellum; the former factor was unaffected by alcohol/cocaine exposure. This study has shown that there appears to be specificity of GABAergic gene groups, defined by covariation in expression, for response to chronic alcohol/cocaine exposure. These findings might have implications for combating stress-related craving and relapse. Public Library of Science 2013-05-22 /pmc/articles/PMC3661725/ /pubmed/23717525 http://dx.doi.org/10.1371/journal.pone.0064014 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Enoch, Mary-Anne
Baghal, Basel
Yuan, Qiaoping
Goldman, David
A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure
title A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure
title_full A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure
title_fullStr A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure
title_full_unstemmed A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure
title_short A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure
title_sort factor analysis of global gabaergic gene expression in human brain identifies specificity in response to chronic alcohol and cocaine exposure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661725/
https://www.ncbi.nlm.nih.gov/pubmed/23717525
http://dx.doi.org/10.1371/journal.pone.0064014
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