Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.

Progressive increases in ethanol consumption is a hallmark of alcohol use disorder (AUD). Persistent changes in brain gene expression are hypothesized to underlie the altered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to pr...

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Autores principales: Maren L Smith, Marcelo F Lopez, Aaron R Wolen, Howard C Becker, Michael F Miles
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Publicado: Public Library of Science (PLoS) 2020
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Acceso en línea:https://doaj.org/article/d3a8f1a18fdb4a32bbaec0a6f6ab9f4a
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spelling oai:doaj.org-article:d3a8f1a18fdb4a32bbaec0a6f6ab9f4a2021-12-02T20:11:29ZBrain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.1932-620310.1371/journal.pone.0233319https://doaj.org/article/d3a8f1a18fdb4a32bbaec0a6f6ab9f4a2020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0233319https://doaj.org/toc/1932-6203Progressive increases in ethanol consumption is a hallmark of alcohol use disorder (AUD). Persistent changes in brain gene expression are hypothesized to underlie the altered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to progressive ethanol consumption, we performed microarray and scale-free network analysis of expression responses in a C57BL/6J mouse model utilizing chronic intermittent ethanol by vapor chamber (CIE) in combination with limited access oral ethanol consumption. This model has previously been shown to produce long-lasting increased ethanol consumption, particularly when combining oral ethanol access with repeated cycles of intermittent vapor exposure. The interaction of CIE and oral consumption was studied by expression profiling and network analysis in medial prefrontal cortex, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, and central nucleus of the amygdala. Brain region expression networks were analyzed for ethanol-responsive gene expression, correlation with ethanol consumption and functional content using extensive bioinformatics studies. In all brain-regions studied the largest number of changes in gene expression were seen when comparing ethanol naïve mice to those exposed to CIE and drinking. In the prefrontal cortex, however, unique patterns of gene expression were seen compared to other brain-regions. Network analysis identified modules of co-expressed genes in all brain regions. The prefrontal cortex and nucleus accumbens showed the greatest number of modules with significant correlation to drinking behavior. Across brain-regions, however, many modules with strong correlations to drinking, both baseline intake and amount consumed after CIE, showed functional enrichment for synaptic transmission and synaptic plasticity.Maren L SmithMarcelo F LopezAaron R WolenHoward C BeckerMichael F MilesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 5, p e0233319 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maren L Smith
Marcelo F Lopez
Aaron R Wolen
Howard C Becker
Michael F Miles
Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
description Progressive increases in ethanol consumption is a hallmark of alcohol use disorder (AUD). Persistent changes in brain gene expression are hypothesized to underlie the altered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to progressive ethanol consumption, we performed microarray and scale-free network analysis of expression responses in a C57BL/6J mouse model utilizing chronic intermittent ethanol by vapor chamber (CIE) in combination with limited access oral ethanol consumption. This model has previously been shown to produce long-lasting increased ethanol consumption, particularly when combining oral ethanol access with repeated cycles of intermittent vapor exposure. The interaction of CIE and oral consumption was studied by expression profiling and network analysis in medial prefrontal cortex, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, and central nucleus of the amygdala. Brain region expression networks were analyzed for ethanol-responsive gene expression, correlation with ethanol consumption and functional content using extensive bioinformatics studies. In all brain-regions studied the largest number of changes in gene expression were seen when comparing ethanol naïve mice to those exposed to CIE and drinking. In the prefrontal cortex, however, unique patterns of gene expression were seen compared to other brain-regions. Network analysis identified modules of co-expressed genes in all brain regions. The prefrontal cortex and nucleus accumbens showed the greatest number of modules with significant correlation to drinking behavior. Across brain-regions, however, many modules with strong correlations to drinking, both baseline intake and amount consumed after CIE, showed functional enrichment for synaptic transmission and synaptic plasticity.
format article
author Maren L Smith
Marcelo F Lopez
Aaron R Wolen
Howard C Becker
Michael F Miles
author_facet Maren L Smith
Marcelo F Lopez
Aaron R Wolen
Howard C Becker
Michael F Miles
author_sort Maren L Smith
title Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
title_short Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
title_full Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
title_fullStr Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
title_full_unstemmed Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
title_sort brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
publisher Public Library of Science (PLoS)
publishDate 2020
url https://doaj.org/article/d3a8f1a18fdb4a32bbaec0a6f6ab9f4a
work_keys_str_mv AT marenlsmith brainregionalgeneexpressionnetworkanalysisidentifiesuniqueinteractionsbetweenchronicethanolexposureandconsumption
AT marceloflopez brainregionalgeneexpressionnetworkanalysisidentifiesuniqueinteractionsbetweenchronicethanolexposureandconsumption
AT aaronrwolen brainregionalgeneexpressionnetworkanalysisidentifiesuniqueinteractionsbetweenchronicethanolexposureandconsumption
AT howardcbecker brainregionalgeneexpressionnetworkanalysisidentifiesuniqueinteractionsbetweenchronicethanolexposureandconsumption
AT michaelfmiles brainregionalgeneexpressionnetworkanalysisidentifiesuniqueinteractionsbetweenchronicethanolexposureandconsumption
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