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Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure.

ABSTRACT: Alcohol use disorder is a chronic relapsing brain disorder and a global health issue. Prolonged high alcohol consumption increases the risk for dependence development, a complex state that includes progressive alterations in brain function. The molecular mechanisms behind these changes remain to be fully disclosed, but several genes show altered expression in various regions of the rat brain even after modest alcohol exposure. The present study utilizes whole-transcriptome sequencing (RNA-seq) to investigate expression changes in the brain nucleus accumbens (NAc), an area of particular interest in addictive disorders, of alcohol consuming rats. The impact on gene expression after eight weeks of moderate voluntary alcohol consumption or voluntary consumption combined with forced excessive exposure was explored in two separate experiments. The results point to a lack of strong and consistent expression alterations in the NAc after alcohol exposure, suggesting that transcriptional effects of alcohol are weak or transient, or occur primarily in brain regions other than NAc.

SUBMITTER: Morud J

PROVIDER: S-EPMC5513432 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure.

Morud Julia J Ashouri Arghavan A Larsson Erik E Ericson Mia M Söderpalm Bo B

PloS one 20170717 7

Alcohol use disorder is a chronic relapsing brain disorder and a global health issue. Prolonged high alcohol consumption increases the risk for dependence development, a complex state that includes progressive alterations in brain function. The molecular mechanisms behind these changes remain to be fully disclosed, but several genes show altered expression in various regions of the rat brain even after modest alcohol exposure. The present study utilizes whole-transcriptome sequencing (RNA-seq) t ...[more]

PMID: 28715440

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Project description:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naÃÂ¯ve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included Ã¢ÂÂnegative regulation of protein kinase activityÃ¢ÂÂ, Ã¢ÂÂanti-apoptosisÃ¢ÂÂ, and Ã¢ÂÂregulation of G-protein-coupled receptor protein signaling pathwayÃ¢ÂÂ. IngenuityÃÂ® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Experiment Overall Design: 10 samples each of control, continuous ethanol and limited access ethanol

Dataset Information

Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure.

Publications

Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure.

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