title: Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice.
abstract: 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.
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France.|Université Paris Descartes, UMR S894, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Stragier
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France.|Université Paris Descartes, UMR S894, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Martin
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France.|Université Paris Descartes, UMR S894, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Davenas
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France.|Université Paris Descartes, UMR S894, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Poilbout
authors.affiliation: Université Paris Descartes, UMR S894, Paris, France.|Pharmacologie de la circulation cérébrale EA 4475, Faculté de pharmacie Université Paris Descartes, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Mongeau
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-2588-0484
authors.initials: R
authors.lastname: Corradetti
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France.|Université Paris Descartes, UMR S894, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Lanfumey
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000187:drug effects*; D016133:Polymerase Chain Reaction
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol