Overexpression of NGF ameliorates ethanol neurotoxicity in the developing cerebellum

Transgenic mice overexpressing NGF in the central nervous system under the control of the glial fibrillary acidic protein (GFAP) promoter were exposed to ethanol via vapor inhalation on postnatal days 4 and 5 (P4-5), the peri od of maximal cerebellar Purkinje cell sensitivity to ethanol. Wild-type co ntrols were exposed in a similar manner. There were no differences in body weight or size following these procedures, but the transgenic brain weights at this age were significantly greater than wild-type controls. In the wil d-type animals, a significant 33.3% ethanol-mediated loss of Purkinje cells in lobule I was detected via unbiased three-dimensional stereological coun ting on P5. In the GFAP-NGF transgenic animals, however, the 17.6% differen ce in Purkinje cell number in control and ethanol-exposed animals was not s ignificant. There was a similar difference in Purkinje cell density in both groups, which did reach statistical significance (-32.7% in wild-type etha nol-treated animals, -17% in transgenic ethanol-exposed animals). These res ults suggest that endogenous overexpression of neurotrophic factors, which have previously been shown to protect against ethanol neurotoxicity in cult ure, can serve a similar protective function in the intact animal. (C) 2000 John Wiley & Sons, Inc.