Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys
Year: 2019
Type: article
Abstract: Despite recent extensive genomic and genetic studies on behavioral responses to ethanol, relatively few new therapeutic targets for the treatment of alcohol use disorder have been validated. Here, we describe a cross-species genomic approach focused on identifying gene networks associated with chronic ethanol consumption. To identify brain mechanisms underlying a chronic ethanol consumption phenotype highly relevant to human alcohol use disorder, and to elucidate potential future therapeutic targets, we conducted a genomic study in a non-human primate model of chronic open-access ethanol consumption. Microarray analysis of RNA expression in anterior cingulate and subgenual cortices from rhesus macaques was performed across multiple cohorts of animals. Gene networks correlating with ethanol consumption or showing enrichment for ethanol-regulated genes were identified, as were major ethanol-related hub genes within these networks. A subsequent consensus module analysis was used to co-analyze monkey data with expression data from a chronic intermittent ethanol vapor-exposure and consumption model in C57BL/6J mice. Ethanol-related gene networks conserved between primates and rodents were enriched for genes involved in discrete biological functions, including; myelination, synaptic transmission, chromatin modification, Golgi apparatus function, translation, cellular respiration, and RNA processing. The myelin-related network, in particular, showed strong correlations with ethanol consumption behavior and displayed marked network reorganization between control and ethanol-drinking animals. Further bioinformatics analysis revealed that these networks also showed highly significant overlap with other ethanol-regulated gene sets. Altogether, these studies provide robust primate and rodent cross-species validation of gene networks associated with chronic ethanol consumption. Our results also suggest potential novel focal points for future therapeutic interventions in alcohol use disorder.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: INIA Stress and Chronic Alcohol Interactions: CORE2: Stress-CIE Drinking Mouse Core, Training Grant in Digestive Diseases and Liver Diseases, Of Mice and Primates: Gene Networks in Excessive Ethanol Consumption and Anxiety, G4976450837, G716289812, Cross-species investigation of gene networks for ethanol-related behaviors, 1/8: INIA Stress and Chronic Alcohol Interactions: Role of Dynorphin/KOR and Oxytocin Systems in Stress-Enhanced Alcohol Drinking, Relapse, and Impaired Behavioral Flexibility, Alcohol Research Center - Treatment and Implications, Support for National Primate Research Center, 6/8: INIA Stress and Chronic Alcohol Interactions: Stress and Ethanol Self Administration in Monkeys, Monkey Alcohol Tissue Research Resource (MATRR)
OpenAlex ID: W2964779492