intermittent ethanol during adolescence leads to lasting behavioral changes in adulthood and alters gene expression and histone methylation in the pfc

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2017
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Abstract
Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC) transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task. As adults, mice were tested for cognitive changes using the novel object recognition task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge ethanol altered ethanol sensitivity in young mice and led to lasting memory deficits in the object recognition test and greater ethanol sensitivity in adulthood. Using genomic profiling of transcripts in the PFC, we found that binge ethanol reduced myelin-related gene expression and altered chromatin modifying genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that ethanol’s actions on histone methylation may be a switch for future transcriptional changes that underlie the behavioral changes lasting into adulthood.
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wolstenholme2017frontiersintermittent Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Jennifer T. Wolstenholme;Jennifer T. Wolstenholme;Tariq Mahmood;Guy M. Harris;Shahroze Abbas;Michael F. Miles;Michael F. Miles;Michael F. Miles
Journal international journal of nanomedicine
Year 2017
DOI
10.3389/fnmol.2017.00307
URL
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00307/full
Keywords
Adolescent genomics prefrontal cortex ethanol neuropsychiatry biological psychiatry epigeneticsneurosciences

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