Ethanol-induced epigenetic regulations at the Bdnf gene in C57BL/6J mice

• Published in: Molecular psychiatry Vol. 20; no. 3; pp. 405 - 412
• Main Authors: Stragier, E, Massart, R, Salery, M, Hamon, M, Geny, D, Martin, V, Boulle, F, Lanfumey, L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2015; Nature Publishing Group
• Subjects: 13/2; 13/51; 38; 38/15; 38/39; 631/337; 82/1; 82/29; 82/51; 82/80; Alcohol; Alcohol, Denatured; Animals; Azepines - pharmacology; Behavioral Sciences; Benzamides - pharmacology; Biological Psychology; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell growth; Cell proliferation; Cell survival; Cell Survival - drug effects; Central Nervous System Depressants - pharmacology; Choice Behavior - drug effects; Chromatin remodeling; Conditioning, Operant; Dentate gyrus; DNA methylation; Drinking - drug effects; Epigenesis, Genetic - drug effects; Epigenetic inheritance; Epigenetics; Ethanol; Ethanol - pharmacology; Exons; Genes; Genetic aspects; Health aspects; Hippocampal plasticity; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Histones - metabolism; Intercellular Signaling Peptides and Proteins - metabolism; Laboratories; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Neural plasticity; Neurogenesis; Neurosciences; original-article; Pharmacotherapy; Physiological aspects; Post-translation; Promoter Regions, Genetic - drug effects; Psychiatry; Receptor, trkB - antagonists & inhibitors; Receptor, trkB - metabolism; Rodents; Stem cells; TrkB receptors; Water consumption; France; Paris France
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2014.38

High ethanol intake is well known to induce both anxiolytic and anxiogenic effects, in correlation with chromatin remodeling in the amygdaloid brain region and deficits in cell proliferation and survival in the hippocampus of rodents. Whether only moderate but chronic ethanol intake in C57BL/6J mice could also have an impact on chromatin remodeling and neuroplasticity was addressed here. Chronic ethanol consumption in a free choice paradigm was found to induce marked changes in the expression of genes implicated in neural development and histone post-translational modifications in the mouse hippocampus. Transcripts encoding neural bHLH activators and those from
Bdnf
exons II, III and VI were upregulated, whereas those from
Bdnf
exon VIII and
Hdacs
were downregulated by ethanol compared with water consumption. These ethanol-induced changes were associated with enrichment in both acetylated H3 at
Bdnf
promoter PVI and trimethylated H3 at PII and PIII. Conversely, acetylated H3 at PIII and PVIII and trimethylated H3 at PVIII were decreased in ethanol-exposed mice. In parallel, hippocampal brain-derived neurotrophic factor (BDNF) levels and TrkB-mediated neurogenesis in the dentate gyrus were significantly enhanced by ethanol consumption. These results suggest that, in C57BL/6J mice, chronic and moderate ethanol intake produces marked epigenetic changes underlying BDNF overexpression and downstream hippocampal neurogenesis.