title: Comparison of the deleterious effects of binge drinking-like alcohol exposure in adolescent and adult mice.
abstract: A major cause of alcohol toxicity is the production of reactive oxygen species generated during ethanol metabolism. The aim of this study was to compare the effect of binge drinking-like alcohol exposure on a panel of genes implicated in oxidative mechanisms in adolescent and adult mice. In adolescent animals, alcohol decreased the expression of genes involved in the repair and protection of oxidative DNA damage such as atr, gpx7, or nudt15 and increased the expression of proapoptotic genes such as casp3. In contrast, in the adult brain, genes activated by alcohol were mainly associated with protective mechanisms that prevent cells from oxidative damage. Whatever the age, iterative binge-like episodes provoked the same deleterious effects as those observed after a single binge episode. In adolescent mice, multiple binge ethanol exposure substantially reduced neurogenesis in the dentate gyrus and impaired short-term memory in the novel object and passive avoidance tests. Taken together, our results indicate that alcohol causes deleterious effects in the adolescent brain which are distinct from those observed in adults. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. The effects of alcohol exposure were investigated on genes involved in oxidative mechanisms. In adolescent animals, alcohol decreased the expression of genes involved in DNA repair, a potential cause of the observed decrease of neurogenesis. In contrast, in the adult brain, alcohol increased the expression of genes associated with antioxidant mechanisms. Apoptosis was increase in all groups and converged with other biochemical alterations to enhance short-term memory impairment in the adolescent brain. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity.
authors.affiliation: INSERM U982, Neurotrophic factors and neuronal differentiation team, Mont-Saint-Aignan, France; International Associated Laboratory Samuel de Champlain, Mont-Saint-Aignan, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Lacaille
authors.forename: Dominique
authors.initials: D
authors.lastname: Duterte-Boucher
authors.forename: Donovan
authors.initials: D
authors.lastname: Liot
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Mickael
authors.initials: M
authors.lastname: Naassila
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
mesh_terms: D000367:Age Factors; D000818:Animals; D063425:Binge Drinking / Q000097:blood* / Q000235:genetics* / Q000523:psychology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
chemical_list: D000431:Ethanol
keywords: adolescent; alcohol; brain; gene regulation; memory impairment; oxidative stress