The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort
| Autor: | Michael F. Miles, Guy M. Harris, Howard C. Becker, Marcelo F. Lopez, Maren L. Smith, Aaron R. Wolen, Andrew D. van der Vaart, Jennifer T. Wolstenholme, Robert W. Williams |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Health (social science) Alcohol Drinking Protein Array Analysis Prefrontal Cortex Nucleus accumbens Biology Toxicology Biochemistry Nucleus Accumbens Article Transcriptome Cohort Studies 03 medical and health sciences Behavioral Neuroscience Mice 0302 clinical medicine Internal medicine Genetic variation Gene expression medicine Animals Gene Regulatory Networks Prefrontal cortex Gene Genetics Regulation of gene expression Inhalation Exposure Ethanol General Medicine Mice Inbred C57BL 030104 developmental biology Endocrinology Neurology Gene Expression Regulation Allostasis Mice Inbred DBA Expression quantitative trait loci Female 030217 neurology & neurosurgery |
| Zdroj: | Alcohol (Fayetteville, N.Y.). 58 |
| ISSN: | 1873-6823 |
| Popis: | The transition from acute to chronic ethanol exposure leads to lasting behavioral and physiological changes such as increased consumption, dependence, and withdrawal. Changes in brain gene expression are hypothesized to underlie these adaptive responses to ethanol. Previous studies on acute ethanol identified genetic variation in brain gene expression networks and behavioral responses to ethanol across the BXD panel of recombinant inbred mice. In this work, we have performed the first joint genetic and genomic analysis of transcriptome shifts in response to chronic intermittent ethanol (CIE) by vapor chamber exposure in a BXD cohort. CIE treatment is known to produce significant and sustained changes in ethanol consumption with repeated cycles of ethanol vapor. Using Affymetrix microarray analysis of prefrontal cortex (PFC) and nucleus accumbens (NAC) RNA, we compared CIE expression responses to those seen following acute ethanol treatment, and to voluntary ethanol consumption. Gene expression changes in PFC and NAC after CIE overlapped significantly across brain regions and with previously published expression following acute ethanol. Genes highly modulated by CIE were enriched for specific biological processes including synaptic transmission, neuron ensheathment, intracellular signaling, and neuronal projection development. Expression quantitative trait locus (eQTL) analyses identified genomic loci associated with ethanol-induced transcriptional changes with largely distinct loci identified between brain regions. Correlating CIE-regulated genes to ethanol consumption data identified specific genes highly associated with variation in the increase in drinking seen with repeated cycles of CIE. In particular, multiple myelin-related genes were identified. Furthermore, genetic variance in or near dynamin3 (Dnm3) on Chr1 at ∼164 Mb may have a major regulatory role in CIE-responsive gene expression. Dnm3 expression correlates significantly with ethanol consumption, is contained in a highly ranked functional group of CIE-regulated genes in the NAC, and has a cis-eQTL within a genomic region linked with multiple CIE-responsive genes. |
| Databáze: | OpenAIRE |
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