PROTECTIVE EFFECT OF EPIDERMAL GROWTH-FACTOR ON GLUTAMATE NEUROTOXICITY IN CULTURED CEREBELLAR NEURONS

The effects of epidermal growth factor (EGF) on glutamate-induced neuronal death were investigated in primary cultures of dissociated cerebellar neurons from fetal rats. Addition of an excess concentration of L-glutamate (5 mM) to the culture medium greatly decreased the number of surviving neurons 24 h later. When EGF was added to the culture medium 20 h prior to exposure to glutamate, glutamate-induced neuronal death was significantly reduced. The protective effects of EGF on glutamate neurotoxicity were concentration-dependent in the range of 0.01-10 ng/ml. When EGF was added 1 h prior to exposure to glutamate, it did not prevent glutamate-induced neuronal death, indicating that a longer exposure period is required for EGF to exert its protective effects. Furthermore, the protective effects of EGF on glutamate neurotoxicity disappeared in the presence of cycloheximide (0.1-mu-M), a protein synthesis inhibitor. These results suggest that EGF can protect brain neurons against glutamate toxicity through some protein synthesis.