title: Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.
abstract: Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of America.
authors: Elizabeth A
authors: EA
authors: Osterndorff-Kahanek
authors: Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors: Howard C
authors: HC
authors: Becker
authors: Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors: Marcelo F
authors: MF
authors: Lopez
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of America.
authors: Sean P
authors: SP
authors: Farris
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of America.
authors: Gayatri R
authors: GR
authors: Tiwari
authors: Pharmacotherapy Education and Research Center, College of Pharmacy, The University of Texas at Austin, Austin, Texas, United States of America.
authors: Yury O
authors: YO
authors: Nunez
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of America.
authors: R Adron
authors: RA
authors: Harris
authors: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of America.
authors: R Dayne
authors: RD
authors: Mayfield
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000431:Ethanol