VULNERABILITY OF CEREBELLAR GRANULE CELLS TO ALCOHOL-INDUCED CELL-DEATH DIMINISHES WITH TIME IN CULTURE

This study examined the effects of alcohol exposure on the viability o f cerebellar granule cells in culture. Continuous alcohol exposure, st arting 1 day after the cultures were established, significantly reduce d granule cell numbers, even with a single day of exposure to an alcoh ol concentration as low as 100 mg/dl. The depletion of cerebellar gran ule cells by alcohol was concentration-dependent (greater loss of cell s at higher alcohol concentrations) and duration-dependent (greater lo ss of cells at longer exposure durations). The loss of granule cells a lso depended on the number of days the granule cells were in culture b efore alcohol exposure. Alcohol was significantly more effective in re ducing the cell numbers of newly established granule cell cultures (1 day in vitro) compared with older cultures (4 or 7 days in vitro). Cel l cycle analysis established that the cerebellar granule cells did not proliferate in culture, indicating that alcohol exposure did not redu ce cell numbers by interfering with cell proliferation in this system. Instead, alcohol-induced killing of the granule cells was the most li kely mechanism to account for the depletion of granule cells in vitro. Granule cell cultures are a useful in vitro model system to study the cellular and molecular aspects of neuronal cell depletion associated with fetal alcohol exposure. The potential role of the N-methyl-D-aspa rtate receptor in this alcohol-induced neuronal cell death is discusse d.