Failure of glycine site NMDA receptor antagonists to protect against L-2-chloropropionic acid-induced neurotoxicity highlights the uniqueness of cerebellar NMDA receptors

Brain Research
P WiddowsonI Wyatt

Abstract

Cultured cerebellar granule cells and cerebellar slices from neonatal rats have been widely used to examine the biochemistry of excitatory amino acid-induced cell death mediated in part by the activation of NMDA receptors. However, the NMDA subunit stoichiometry, producing functional NMDA receptors is different in cultured granule cells, neonatal and adult rat cerebellum as compared to the NMDA receptors in forebrain regions. We have used the L-2-chloropropionic acid (L-CPA) (750 mg/kg) model of NMDA-mediated selective cerebellar granule cell necrosis in vivo to examine the role of the glycine binding site and possible effect of the NR2C subunit (which is largely expressed only in the cerebellum) on granule cell necrosis. The abilities of various NMDA receptor antagonists were examined in vivo to determine the relative contribution of both glutamate and glycine sites involved in the L-CPA-induced neurotoxicity. The potent neuroprotective, non-competitive NMDA receptor antagonist dizocilpine (MK-801) was compared with glutamate and glycine site NMDA antagonists. We have examined a number of markers for the L-CPA-induced granule cell necrosis. The L-CPA-induced reduction in cerebellar aspartate and glutamate concentrations were u...Continue Reading

References

Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A M Marini, S M Paul
Jan 1, 1990·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·R BalázsO S Jørgensen
Mar 24, 1994·Nature·M FarrantS G Cull-Candy

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