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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Choi, D. W. Neuron 1, 623–634 (1988).
Olney, J. W. Drug Dev. Res. 17, 299–319 (1989).
Meldrum, B. S. & Garthwaite, J. Trends pharmac. Sci. 11, 379–387 (1990).
Rosen, D. R. et al. Nature 362, 59–62 (1993).
Saez, J. C., Kessler, J. A., Bennett, M. V. L. & Spray, D. C. Proc. natn. Acad. Sci. U.S.A. 84, 3056–3059 (1987).
Monyer, H., Hartley, D. M. & Choi, D. W. Neuron 5, 121–126 (1990).
Pellegrini-Giampietro, D. E., Cherici, G., Alesiani, M., Carla, V. & Moroni, F. J. Neurosci. 10, 1035–1041 (1990).
Finkelstein, E., Rosen, G. M. & Rauckman, E. J. Arch. Biochem. Biophys. 200, 1–16 (1980).
Dumuis, A., Sebben, M., Haynes, H., Pin, J.-P. & Bockaert, J. Nature 336, 68–70 (1988).
Rosen, G. M. & Finkelstein, E. Adv. free Rad. Biol. Med. 1, 345–375 (1985).
Rosen, G. M. & Turner, M. J. III, J. med. Chem. 31, 428–432 (1988).
Pou, S. et al. Analyt. Biochem. 177, 1–6 (1989).
Didier, M., Heaulme, M., Gonalons, N., Soubrié, P. & Pin, J.-P. Eur. J. Pharmac. 224, 57–65 (1993).
Mayer, M. L. & Miller, R. J. Trends Neurosci. 11, 254–260 (1990).
Traystman, R. J., Kirsch, J. R. & Koehler, R. C. J. appl. Physiol. 71, 1185–1195 (1991).
Heinzel, B., John, M., Klatt, P., Böhme, E. & Mayer, B. Biochem. J. 281, 627–630 (1992).
Pou, S., Pou, W. S., Bredt, D. S., Snyder, S. H. & Rosen, G. M. J. biol. Chem. 267, 24173–24176 (1992).
Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 88, 6368–6371 (1992).
Lerner-Natoli, M., Rondouin, G., de Bock, F. & Bockaert, J. NeuroReport 3, 1109–1112 (1992).
Nowicki, J. P., Duval, D., Poignet, H. & Scatton, B. Eur. J. Pharmac. 204, 339–340 (1992).
Moncada, C., Lekieffre, D., Arvin, B. & Meldrum, B. NeuroReport 3, 530–532 (1992).
Pauwels, P. J. & Leysen, J. E. Neurosci. Lett. 143, 27–30 (1992).
Garthwaite, J. Trends Neurosci. 14, 60–67 (1991).
Bredt, D. S. & Snyder, S. H. Neuron 8, 3–11 (1992).
Van Vliet, B. J. et al. J. Neurochem. 52, 1229–1239 (1989).
Didier, M., Heaulme, M., Soubrié, P., Bockaert, J. & Pin, J.-P. J. neurosci. Res. 27, 25–35 (1990).
Lafon-Cazal, M., Bougault, I., Steinberg, R., Pin, J. P. & Bockaert, J. Brain Res. 593, 63–68 (1992).
Favaron, M. et al. Proc. natn. Acad. Sci. U.S.A. 87, 1983–1987 (1989).
Marin, P., Lafon-Cazal, M. & Bockaert, J. Eur. J. Neurosci. 4, 425–432 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/364535a0
This article is cited by
-
Effects of chronic methamphetamine exposure on rewarding behavior and neurodegeneration markers in adult mice
Psychopharmacology (2023)
-
Inhibitors of Src Family Kinases, Inducible Nitric Oxide Synthase, and NADPH Oxidase as Potential CNS Drug Targets for Neurological Diseases
CNS Drugs (2021)
-
Triclosan-Evoked Neurotoxicity Involves NMDAR Subunits with the Specific Role of GluN2A in Caspase-3-Dependent Apoptosis
Molecular Neurobiology (2019)
-
Nicotinamide reverses behavioral impairments and provides neuroprotection in 3˗nitropropionic acid induced animal model ofHuntington’s disease: implication of oxidative stress˗ poly(ADP˗ ribose) polymerase pathway
Metabolic Brain Disease (2018)
-
Caffeine Prevents Memory Impairment Induced by Hyperhomocysteinemia
Journal of Molecular Neuroscience (2018)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.