PMID- 26670281 OWN - NLM STAT- MEDLINE DCOM- 20160926 LR - 20240326 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 5 IP - 12 DP - 2015 Dec 15 TI - Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice. PG - e696 LID - 10.1038/tp.2015.183 [doi] AB - Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol. FAU - Stragier, E AU - Stragier E AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France. AD - Universite Paris Descartes, UMR S894, Paris, France. FAU - Martin, V AU - Martin V AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France. AD - Universite Paris Descartes, UMR S894, Paris, France. FAU - Davenas, E AU - Davenas E AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France. AD - Universite Paris Descartes, UMR S894, Paris, France. FAU - Poilbout, C AU - Poilbout C AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France. AD - Universite Paris Descartes, UMR S894, Paris, France. FAU - Mongeau, R AU - Mongeau R AD - Universite Paris Descartes, UMR S894, Paris, France. AD - Pharmacologie de la circulation cerebrale EA 4475, Faculte de pharmacie Universite Paris Descartes, Paris, France. FAU - Corradetti, R AU - Corradetti R AUID- ORCID: 0000-0002-2588-0484 AD - Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. FAU - Lanfumey, L AU - Lanfumey L AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France. AD - Universite Paris Descartes, UMR S894, Paris, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151215 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 RN - 0 (Central Nervous System Depressants) RN - 3K9958V90M (Ethanol) SB - IM MH - Animals MH - Behavior, Animal/drug effects MH - Central Nervous System Depressants/*pharmacology MH - Cognition/*drug effects MH - Ethanol/administration & dosage/*pharmacology MH - Hippocampus/*drug effects MH - Immunoblotting MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Models, Animal MH - Neuronal Plasticity/*drug effects MH - Polymerase Chain Reaction PMC - PMC5068583 EDAT- 2015/12/17 06:00 MHDA- 2016/09/27 06:00 PMCR- 2015/12/01 CRDT- 2015/12/17 06:00 PHST- 2015/05/11 00:00 [received] PHST- 2015/09/23 00:00 [revised] PHST- 2015/10/09 00:00 [accepted] PHST- 2015/12/17 06:00 [entrez] PHST- 2015/12/17 06:00 [pubmed] PHST- 2016/09/27 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - tp2015183 [pii] AID - 10.1038/tp.2015.183 [doi] PST - epublish SO - Transl Psychiatry. 2015 Dec 15;5(12):e696. doi: 10.1038/tp.2015.183.