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.
Sohn
S
S
Laboratory of Cell Biology, Institute for Medical Sciences, Kyungkido, South Korea.
Kim
E Y
EY
Gwag
B J
BJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects; D005333:Fetus; D018698:Glutamic Acid / Q000633:toxicity*; D051379:Mice; D008854:Microscopy, Electron; D009336:Necrosis
D002843:Chromatin; D018698:Glutamic Acid