Article

Neurochemical Research

, Volume 28, Issue 2, pp 259-269

First online:

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

  • Jerzy W. LazarewiczAffiliated withDepartment of Neurochemistry, Medical Research Centre, Polish Academy of Sciences Email author 
  • , Apolonia ZiembowiczAffiliated withDepartment of Neurochemistry, Medical Research Centre, Polish Academy of Sciences
  • , Ewa MatyjaAffiliated withDepartment of Neuropathology, Medical Research Centre, Polish Academy of Sciences
  • , Aleksandra StafiejAffiliated withDepartment of Neurochemistry, Medical Research Centre, Polish Academy of Sciences
  • , Elzbieta ZieminskaAffiliated withDepartment of Neurochemistry, Medical Research Centre, Polish Academy of Sciences

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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.

Calcium cylclosporin A hippocampus homocysteine mGluR microdialysis NMDA