Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The mechanism of kainic acid neurotoxicity

Abstract

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.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  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 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Garthwaite, J., Garthwaite, G. The mechanism of kainic acid neurotoxicity. Nature 305, 138–140 (1983). https://doi.org/10.1038/305138a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/305138a0

Further reading

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing