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BINGE ALCOHOL CONSUMPTION IN ADOLESCENT AND ADULT MICE DIFFERENTIALLY REMODELS THE BRAIN TRANSCRIPTOME
Author(s) -
Owen Julie A.,
Velasquez Oscar,
Levin Patricia S.,
Wang Yan,
Krishnan Harish,
Atkinson Nigel S.,
Bergeson Susan E.
Publication year - 2008
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2008.00689_8.x
Subject(s) - transcriptome , chromatin immunoprecipitation , binge drinking , epigenetics , microarray , biology , gene expression , alcohol , genetics , psychology , alcohol consumption , gene , promoter , biochemistry
Alcohol abuse in pre‐teens and teenagers continues to be a considerable problem in the United States. Not only can brain injury result, but also several studies have now cemented the role of underage drinking in an approximate 5‐fold increased risk for development of alcoholism. The mechanism by which the change in susceptibility occurs is not understood. Therefore, a mouse model of high alcohol consumption was utilized to further include the ability to test the consequences of differential drinking between adolescent and adult animals. Using genetically defined C57BL/6J x FVB/NJ F1 hybrid mice and a “Drinking in the Dark” (DID) protocol, we determined that young mice will drink more than their adult counterparts. Gene expression analysis by cDNA microarray hybridization of brain revealed significant differences in pathway regulation and an age‐apparent left shift of overall transcription by alcohol. Over‐represented transcription factor binding site usage following alcohol exposure was readily apparent in adult, but not adolescent brain. Epigenetic consequences were also uncovered. Chromatin immunoprecipitation (ChIP) analysis showed that alcohol changed the gene expression of Scn4b , a sodium channel beta subunit that modulates the kinetics of firing, through a mechanism involving the acetylation of histone H4. These findings indicate a clear age‐related difference in brain transcriptome plasticity following binge alcohol drinking.