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The mechanism of kainic acid neurotoxicity


The putative excitatory transmitters glutamate and aspartate, as well as their excitatory analogues, can kill neurones in the central nervous system and may thus be involved in the pathogenesis of various neurodegenerative disorders1. Several studies have suggested that postsynaptic receptors are important in the mechanism of toxicity2. However, presynaptic factors might also be involved because, in some brain areas, the neurotoxicity of kainate (a potent structural analogue of glutamate) is greatly reduced following elimination of afferent excitatory innervation3–6, even though the postsynaptic excitatory potency of kainate may be unaltered in these conditions7. The supply of glutamate from the afferent nerve endings has been suggested to be a necessary factor3,6,8. Recently, Ferkany, Zaczec and Coyle9 concluded from studies on slices of mouse cerebellum that kainate activates presynaptic kainate receptors on parallel fibre terminals to release glutamate and that it is the postsynaptic interaction between kainate and the released amino acid that is instrumental in causing neuronal necrosis. The more direct evidence we report here does not support these conclusions.

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  1. Coyle, J. T. et al. Neurosci. Res. Prog. Bull. 19, 329–427 (1981).

    Google Scholar 

  2. Olney, J. W. in Kainic Acid as a Tool in Neurobiology (eds McGeer, E. G., Olney, J. W. & McGeer, P. L.) 95–121 (Raven, New York, 1978).

    Google Scholar 

  3. Biziere, K. & Coyle, J. T. Neurosci. Lett. 8, 303–310 (1978).

    CAS  Article  Google Scholar 

  4. McGeer, E. G., McGeer, P. L. & Singh, K. Brain Res. 139, 381–383 (1978).

    CAS  Article  Google Scholar 

  5. Kohler, C., Schwarcz, R. & Fuxe, Neurosci. Lett. 10, 241–246 (1978).

    CAS  Article  Google Scholar 

  6. Streit, P., Stella, M. & Cuenod, M. Brain Res. 187, 45–57 (1980).

    Google Scholar 

  7. McLennan, H. Neurosci. Lett. 18, 313–316 (1980).

    CAS  Article  Google Scholar 

  8. McGeer, E. G. & McGeer, P. L. Int. Rev. Neurobiol. 22, 173–204 (1981).

    CAS  Article  Google Scholar 

  9. Ferkany, J. W., Zaczec, R. & Coyle, J. T. Nature 298, 757–759 (1982).

    ADS  CAS  Article  Google Scholar 

  10. Garthwaite, J., Woodhams, P. L., Collins, M. J. & Balazs, R. Brain Res. 173, 373–377 (1979).

    CAS  Article  Google Scholar 

  11. Garthwaite, J. & Wilkin, G. P. Neuroscience 7, 2499–2514 (1982).

    CAS  Article  Google Scholar 

  12. Okamoto, K. & Quastel, J. H. Proc. R. Soc. B 184, 83–90 (1973).

    ADS  CAS  Google Scholar 

  13. Garthwaite, J. & Gilligan, G. J. Neuroscience (in the press).

  14. Ferkany, J. W. & Coyle, J. T. J. Pharmac. exp. Ther. 255, 399–406 (1983).

    Google Scholar 

  15. Krespan, B., Berl, S. & Nicklas, W. J. J. Neurochem. 38, 509–518 (1982).

    CAS  Article  Google Scholar 

  16. Monaghan, D. T. & Cotman, C. W. Brain Res. 252, 91–100 (1982).

    CAS  Article  Google Scholar 

  17. Garthwaite, J. Neuroscience 7, 2491–2497 (1982).

    CAS  Article  Google Scholar 

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Garthwaite, J., Garthwaite, G. The mechanism of kainic acid neurotoxicity. Nature 305, 138–140 (1983).

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