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Ganglioside GM1 preventsN-methyl-d-aspartate neurotoxicity in rabbit hippocampus in vivo

Effects on calcium homeostasis
  • Jerzy W. Łazarewicz
  • Elżbieta Salińska
  • Ewa Matyja
Original Articles

Abstract

Microdialysis was used to apply 1 mM N-methyl-d-aspartate (NMDA) for 20 min to the hippocampus of rabbits, control and pretreated with GM1 ganglioside (im injections of 30 mg/kg for 3d, twice a day). Concentrations of ionized Ca2+ and 6-keto prostaglandin F (6-keto PGF)-immunoreactive material in the dialyzates and45Ca and [14C]sucrose efflux from the prelabeled hippocampus were determined. After 24 h, the morphology of the hippocampal neurons was examined. In control animals, the application of NMDA resulted in 25% decrease in Ca2+ concentration and in 1000% increase in 6-keto PGF concentration in the dialyzates. A 30% decrease in45Ca efflux was accompanied by 20% increase in [14C]sucrose efflux, reflecting a corresponding reduction of the extracellular space volume. A degeneration of CA1 pyramidal neurons in the vicinity of a microdialysis probe was observed. In GM1-treated rabbits the NMDA-induced decrease in Ca2+ concentrations in the dialyzates was not reduced significantly, whereas a 70% stimulation of45Ca efflux was noted, with a concomitant 40% reduction of 6-keto-PG F release. NMDA-evoked increase in [14C]sucrose efflux did not differ from the control. In these animals CA1 neurons were well preserved. These results indicate that the pretreatment with GM1 results in activation of calcium extrusion from the NMDA-stimulated rabbit hippocampal neurons that alleviates destabilization of calcium homeostasis and reduces NMDA-evoked neuronal injury.

Index Entries

Calcium GM1 ganglioside hippocampus in vivo study 6-keto prostaglandin F microdialysis morphology NMDA neurotoxicity rabbit sucrose space volume 

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Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • Jerzy W. Łazarewicz
    • 1
  • Elżbieta Salińska
    • 1
  • Ewa Matyja
    • 2
  1. 1.Department of Neurochemistry, Medical Research CentrePolish Academy of SciencesWarsawPoland
  2. 2.Department of Neuropathology, Medical Research CentrePolish Academy of SciencesWarsawPoland

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