title: Bcl-2 overexpression protects the neonatal cerebellum from ethanol neurotoxicity.
abstract: The developing nervous system is extremely sensitive to ethanol, and exposure often produces a condition known as the fetal alcohol syndrome. Although mechanisms underlying developmental ethanol toxicity have long been sought, they remain poorly understood. In this study, we examined the ability of the cell death repressor gene bcl-2 to protect against ethanol neurotoxicity. Transgenic mice overexpressing bcl-2 in neurons were exposed to ethanol vapor on postnatal days 4 and 5, which is the peak period of vulnerability of cerebellar Purkinje cells to ethanol. While exposure of wild-type animals to ethanol resulted in significant loss of Purkinje cells by P5, similar exposure of homozygous and heterozygous transgenics had no effect on the number of these neurons. This study suggests that bcl-2 can protect neurons from ethanol neurotoxicity and that modulation of cell death effector or repressor gene products may play a significant role in developmental ethanol neurotoxicity.
authors.affiliation: Department of Neuroscience, University of Florida Brain Institute, Center for Alcohol Research, University of Florida College of Medicine, Gainesville, FL 32610-0244, USA.heaton@ufbi.ufledu
authors.forename: M B
authors.initials: MB
authors.lastname: Heaton
authors.forename: D B
authors.initials: DB
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Paiva
authors.forename: T
authors.initials: T
authors.lastname: Gibbs
authors.forename: O
authors.initials: O
authors.lastname: Bernard
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D019254:Genes, bcl-2; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009498:Neurotoxins / Q000633:toxicity*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D000431:Ethanol