ETHANOL PROMOTES APOPTOSIS IN CEREBELLAR GRANULE CELLS BY INHIBITING THE TROPHIC EFFECT OF NMDA

When primary cultures of cerebellar granule neurons are grown in a phy siological concentration of KCI (5 mM) they undergo apoptosis, which c an be prevented by growing the cells in the presence of N-methyl-D-asp artate (NMDA). We now show that ethanol inhibits this trophic effect o f NMDA, i.e., promotes apoptosis, and also inhibits the NMDA-induced i ncrease in intracellular Ca2+ concentration in cells grown in 5 mM KCI . Both effects of ethanol show a similar concentration dependence and are reversed by a high concentration of glycine, the coagonist at the NMDA receptor. The data suggest that the effect of ethanol on apoptosi s is mediated, at least in part, by inhibition of NMDA receptor functi on. This effect of ethanol to increase apoptosis could contribute to t he previously described in vivo sensitivity of the developing cerebell um to ethanol-induced damage.