NERVE GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR PROTECT RAT CEREBELLAR GRANULE CELLS IN CULTURE AGAINST ETHANOL-INDUCED CELL-DEATH

Neuronal cell loss is one of the most debilitating effects of fetal et hanol exposure. Cultures of cerebellar granule cells are a useful mode l to investigate ethanol neurotoxicity, because ethanol depletes cell numbers in these cultures, which also occurs in vivo. The primary goal of the present study was to identify and characterize agents that can ameliorate the ethanol-induced cell death that occurs in this culture system. Growth factors, such as nerve growth factor (NGF), basic fibr oblast growth factor (bFGF), epidermal growth factor (EGF), and insuli n-like growth factor-1 (IGF-I) can prevent neuronal degeneration after toxic insult in various experimental paradigms. These growth factors were investigated in the current study to determine whether or not the y can mitigate ethanol-induced death of cerebellar granule cells in cu lture. Results indicate that NGF and bFGF significantly reduced the et hanol-induced cell loss. Both the NGF- and bFGF-mediated neuroprotecti on required protein and RNA synthesis, because actinomycin D (RNA synt hesis inhibitor) and cycloheximide (protein synthesis inhibitor) block ed their neuroprotective effects. In addition to its neuroprotective e ffect, bFGF also had a neurotrophic effect and could enhance cell surv ival in the absence of ethanol exposure. NGF did not have a neurotroph ic effect. Neither EGF nor IGF-I was neuroprotective, although the lat ter did have a substantial neurotrophic effect. In conclusion, bFGF an d NGF have long been recognized for their role in enhancing neuronal c ell survival and differentiation. This study suggests that these growt h factors can also provide neuroprotection against ethanol-induced cel l death.