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N ‐Methyl‐ d ‐Aspartate Receptor Desensitisation Is Neuroprotective by Inhibiting Glutamate‐Induced Apoptotic‐Like Death
Author(s) -
Wood Anita M.,
Bristow David R.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020677.x
Subject(s) - nmda receptor , glutamate receptor , excitotoxicity , neuroprotection , programmed cell death , pharmacology , glutamic acid , receptor , metabotropic glutamate receptor 6 , biology , microbiology and biotechnology , neuroscience , chemistry , apoptosis , metabotropic glutamate receptor , biochemistry , amino acid
Glutamate excitotoxicity is implicated in several neurodegenerative diseases; consequently, considerable effort has been made to elucidate neuroprotective mechanisms against such toxicity. N ‐Methyl‐ d ‐aspartate (NMDA) receptor desensitisation is one potential mechanism for controlling glutamate‐mediated neuronal cell death. Pretreatment of rat cerebellar granule cells with subtoxic concentrations of NMDA caused a marked reduction in the calcium signals generated by subsequent glutamate stimulation, and, furthermore, this receptor desensitisation was coupled to a reduction in glutamate‐induced apoptotic‐like death. These effects were reduced by either d ‐2‐amino‐5‐phosphonopentanoic acid, an NMDA receptor antagonist, or cyclosporin A, an inhibitor of calcineurin. Thus, the results support a role for receptor desensitisation in protection from glutamate‐mediated apoptotic‐like neuronal cell death.