BAPTA-AM AND ETHANOL PROTECT CEREBELLAR GRANULE NEURONS FROM THE DESTRUCTIVE EFFECT OF THE WEAVER GENE

The mechanisms by which the weaver gene (Reeves et al., 1989; Patil et al., 1995) inhibits neurite extension and/or induces death of the gra nule neurons in homozygous weaver mouse cerebellum are not presently u nderstood, Here we show that BAPTA-AM and ethanol, which either reduce cytosolic levels of free calcium or prevent calcium entry, promote ne urite outgrowth of the weaver neurons similar to the L-type calcium ch annel blocker verapamil (Liesi and Wright, 1996), Importantly, BAPTA-A M, ethanol, and verapamil not only restore neurite outgrowth of the we aver neurons but adjust their depolarized resting membrane potentials to the levels of normal neurons, These results indicate that calcium-d ependent mechanisms mediate the action of the weaver gene and that the weaver neurons can be normalized by blocking this calcium effect, We further report that BAPTA-AM and verapamil also have a neuroprotective effect on normal neurons exposed to high concentrations of ethanol. W e suggest that verapamil should be evaluated as a drug for treatment o f alcohol-induced brain damage and neurodegenerative disorders. (C) 19 97 Wiley-Liss, Inc.