NMDA PREVENTS ALCOHOL-INDUCED NEURONAL CELL-DEATH OF CEREBELLAR GRANULE CELLS IN CULTURE

Neuronal cell loss is one of the most debilitating effects of alcohol exposure during development of the nervous system, In this study, prim ary cultures of neuronal cells (cerebellar granule cells) were used to examine mechanisms of alcohol-induced neuronal cell death. Previously , we established that (Pantazis et al., Alcohol Clin Exp Res 17:1014-1 021, 1993): (1) alcohol exposure caused neuronal cell death in culture s of cerebellar granule cells and this cell loss was both time-depende nt and dose-dependent; and (2) the vulnerability of cerebellar granule cells to alcohol-induced loss changed with the length of time the cel ls were in culture before initiating alcohol exposure-that is, younger cultures (1 day in vitro) were much more susceptible to alcohol-induc ed neuronal cell death than older cultures (4 or 7 days in vitro), The primary goal of the present study was to examine the potential role o f the NMDA receptor in alcohol-induced death of cerebellar granule cel ls in culture, Experiments were performed to test the hypothesis that the alcohol-induced death of cerebellar granule cells can be prevented or reduced by NMDA treatment. Our results indicate that stimulation o f the NMDA receptor has a neuroprotective effect and can significantly reduce the alcohol-induced neuronal cell death of newly established c erebellar granule cell cultures, This neuroprotective effect of NMDA i s blocked by 2-amino-5-phosphonovalerate, a competitive inhibitor of t he NMDA receptor, confirming that this neuroprotective effect is media ted via the NMDA receptor. This is the first report that alcohol's neu rotoxic effect can be ameliorated by activation of the NMDA receptor.