Glutamate neurotoxicity in mouse cortical neurons: atypical necrosis with DNA ladders and chromatin condensation.

The possibility that glutamate may induce neuronal apoptosis was examined in cultured cortical neurons. Neurons underwent widespread death 24 h following exposure to 50 microM glutamate. The glutamate neurotoxicity was blocked by inclusion of the glutamate antagonists, 10 microM MK-801 and 50 microM 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 necrosis. With blockade of excitotoxicity by addition of 10 microM MK-801 and 50 microM CNQX, cortical neurons exposed to 2 mM glutamate underwent necrosis morphologically identical to excitotoxicity but sensitive to 100 microM trolox, an antioxidant, suggesting that high doses of glutamate produce oxidative neuronal necrosis via non-receptor-mediated mechanisms. Interestingly, internucleosomal DNA fragmentation and chromatin condensation were observed in the course of glutamate-induced neuronal necrosis.