Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Animals, Newborn
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Apoptosis / drug effects*
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Calcineurin Inhibitors
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Calcium / metabolism*
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Cells, Cultured
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Cerebellum / cytology*
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Cerebellum / physiology
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Chromatin / drug effects
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Chromatin / ultrastructure
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Cyclosporine / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / pharmacology*
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Kinetics
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N-Methylaspartate / toxicity*
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Neurons / cytology*
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Neurons / drug effects
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Neurons / physiology
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Neuroprotective Agents / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / physiology*
Substances
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Calcineurin Inhibitors
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Chromatin
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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Receptors, N-Methyl-D-Aspartate
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Glutamic Acid
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N-Methylaspartate
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2-Amino-5-phosphonovalerate
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Cyclosporine
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Calcium