INVOLVEMENT OF N-METHYL-D-ASPARTATE RECEPTOR AND FREE-RADICAL IN HOMOCYSTEINE-MEDIATED TOXICITY ON RAT CEREBELLAR GRANULE CELLS IN CULTURE

The present study investigates the possible mechanism responsible for the neurotoxicity of D,L-homocysteine in primary culture of rat cerebe llar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocystei ne treatment. D,L-Homocysteine (>300 mu M; 16-22 h) induced the releas e of lactate dehydrogenase from the cells in a concentration-dependent manner. The N-methyl-D-aspartate (NMDA) antagonist (+/-)-2-amino-5-ph osphonopentanoic acid (APV) partially blocked the homocysteine-mediate d neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-n itroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediat ed toxicity. The homocysteine-mediated neurotoxicity was mostly preven ted by the co-administration of superoxide dismutase and catalase or c atalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free r adicals.