GLUTAMATE NEUROTOXICITY IN MOUSE CORTICAL-NEURONS - ATYPICAL NECROSISWITH DNA LADDERS AND CHROMATIN CONDENSATION

The possibility that glutamate may induce neuronal apoptosis was exami ned in cultured cortical neurons. Neurons underwent widespread death 2 4 h following exposure to 50 mu M glutamate. The glutamate neurotoxici ty was blocked by inclusion of the glutamate antagonists, 10 mu M MK-8 01 and 50 mu M CNQX. The death was characterized by swelling cell body and bursting cytoplasmic membrane in the early phase of degeneration, suggesting that glutamate produces receptor-mediated excitotoxic necr osis. With blockade of excitotoxicity by addition of 10 mu M MK-801 an d 50 mu M CNQX, cortical neurons exposed to 2 mM glutamate underwent n ecrosis morphologically identical to excitotoxicity but sensitive to 1 00 mu M trolox, an antioxidant, suggesting that high doses of glutamat e produce oxidative neuronal necrosis via non-receptor-mediated mechan isms. Interestingly, internucleosomal DNA fragmentation and chromatin condensation were observed in the course of glutamate-induced neuronal necrosis. (C) 1998 Elsevier Science Ireland Ltd.