Neurochemical Research

, Volume 28, Issue 2, pp 259–269

Homocysteine-Evoked 45Ca Release in the Rabbit Hippocampus Is Mediated by Both NMDA and Group I Metabotropic Glutamate Receptors: In Vivo Microdialysis Study

Authors

    • Department of NeurochemistryMedical Research Centre, Polish Academy of Sciences
  • Apolonia Ziembowicz
    • Department of NeurochemistryMedical Research Centre, Polish Academy of Sciences
  • Ewa Matyja
    • Department of NeuropathologyMedical Research Centre, Polish Academy of Sciences
  • Aleksandra Stafiej
    • Department of NeurochemistryMedical Research Centre, Polish Academy of Sciences
  • Elzbieta Zieminska
    • Department of NeurochemistryMedical Research Centre, Polish Academy of Sciences
Article

DOI: 10.1023/A:1022329317218

Cite this article as:
Lazarewicz, J.W., Ziembowicz, A., Matyja, E. et al. Neurochem Res (2003) 28: 259. doi:10.1023/A:1022329317218

Abstract

This in vivo microdialysis study compared the effects of NMDA and d,l-homocysteine (Hcy) administered via dialysis medium on 45Ca efflux from prelabeled rabbit hippocampus. Application of these agonists evoked dose-dependent, and sensitive to MK-801, opposite effects: NMDA decreased the 45Ca radioactivity in the dialysate, whereas Hcy induced the release of 45Ca. The latter effect was potentiated by glycine, inhibited by the antagonist of group I metabotropic glutamate receptors (mGluR) LY367385, and mimicked by t-ADA, an agonist of these receptors. Electron microscopic examination of pyramidal neurones in the CA1 sector of the hippocampus in the vicinity of the microdialysis probe after NMDA application demonstrated swelling of mitochondria, which was prevented by cyclosporin A. This study shows, for the first time, Hcy-induced activation of both group I mGluR and NMDA receptors, which may play a role in acute Hcy neurotoxicity. We present new applications of brain microdialysis in studies on excitotoxicity and neuroprotection.

Calciumcylclosporin AhippocampushomocysteinemGluRmicrodialysisNMDA
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© Plenum Publishing Corporation 2003