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

Glutamate neurotoxicity in mouse cortical neurons: atypical necrosis with DNA ladders and... The possibility that glutamate may induce neuronal apoptosis was examined in cultured cortical neurons. Neurons underwent widespread death 24 h following exposure to 50 μ M glutamate. The glutamate neurotoxicity was blocked by inclusion of the glutamate antagonists, 10 μ M MK-801 and 50 μ 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 necrosis. With blockade of excitotoxicity by addition of 10 μ M MK-801 and 50 μ M CNQX, cortical neurons exposed to 2 mM glutamate underwent necrosis morphologically identical to excitotoxicity but sensitive to 100 μ M 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuroscience Letters Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 1998 Elsevier Science Ireland Ltd
ISSN
0304-3940
D.O.I.
10.1016/S0304-3940(97)00936-1
Publisher site
See Article on Publisher Site

Abstract

The possibility that glutamate may induce neuronal apoptosis was examined in cultured cortical neurons. Neurons underwent widespread death 24 h following exposure to 50 μ M glutamate. The glutamate neurotoxicity was blocked by inclusion of the glutamate antagonists, 10 μ M MK-801 and 50 μ 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 necrosis. With blockade of excitotoxicity by addition of 10 μ M MK-801 and 50 μ M CNQX, cortical neurons exposed to 2 mM glutamate underwent necrosis morphologically identical to excitotoxicity but sensitive to 100 μ M 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.

Journal

Neuroscience LettersElsevier

Published: Jan 16, 1998

References

  • Apoptosis of human lymphocytes in the absence or presence of internucleosomal DNA cleavage
    Marini, M.; Musiani, D.; Sestili, P.; Cantoni, O.
  • NMDA and kainate induce internucleosomal DNA cleavage associated with both apoptotic and necrotic cell death in the neonatal rat brain
    van Lookeren Campagne, M.; Lucassen, P.J.; Vermeulen, J.P.; Balazs, R.

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