Bcl-2 overexpression protects the neonatal cerebellum from ethanol neurotoxicity

The developing nervous system is extremely sensitive to ethanol, and exposu re 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 neurotoxicit y. 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 animal s to ethanol resulted in significant loss of Purkinje cells by pi, similar exposure of homozygous and heterozygous transgenics had no effect on the nu mber of these neurons. This study suggests that bcl-2 can protect neurons f rom ethanol neurotoxicity and that modulation of cell death effector or rep ressor gene products may play a significant role in developmental ethanol n eurotoxicity. (C) 1999 Elsevier Science B.V. All rights reserved.