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NMDA-dependent superoxide production and neurotoxicity

Nature volume 364, pages 535–537 (1993)Cite this article

Abstract

NEURONAL injury resulting from acute brain insults and some neurodegenerative diseases implicates N-methyl-D-aspartate (NMDA) glutamate receptors1–4. The fact that antioxidants reduce some types of brain damage suggests that oxygen radicals may have a role5–7. It has been shown that mutations in Cu/Zn-superoxide dismutase (SOD), an enzyme catalysing superoxide (O·-2) detoxification in the cell, are linked to a familial form of amyotrophic lateral sclerosis (ALS)4. Here we report that O·-2 is produced upon NMDA receptor stimulation in cultured cerebellar granule cells. Electron paramagnetic resonance was used to assess O·-2 production that was due in part to the release of arachidonic acid. Activation of kainic acid receptors, or voltage-sensitive Ca2+ channels, did not produce detectable O·-2. We also find that the nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), used as a spin trap, is more efficient than the nitric oxide synthase inhibitor, L-NG-nitroarginine, in reducing NMDA-induced neuronal death in these cultures.

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Authors and Affiliations

  1. Centre CNRS-INSERM de Pharmacologie-Endocrinologie, rue de la Cardonille, 34094, Montpellier, Cedex 5, France

    Mireille Lafon-Cazal & Joel Bockaert

  2. CRIPDOM, PO Box 43, 34172, Castelnau-le Lez Cedex, France

    Sylvia Pietri & Marcel Culcasi

  3. SREP-CNRS URA 1412, Université de Provence, 13397, Marseille, Cedex 13, France

    Sylvia Pietri & Marcel Culcasi

Authors
  1. Mireille Lafon-Cazal
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  2. Sylvia Pietri
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  3. Marcel Culcasi
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  4. Joel Bockaert
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Lafon-Cazal, M., Pietri, S., Culcasi, M. et al. NMDA-dependent superoxide production and neurotoxicity. Nature 364, 535–537 (1993). https://doi.org/10.1038/364535a0

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