1379868

Failure of a protein synthesis inhibitor to modify glutamate receptor-mediated neurotoxicity in vivo.

Article date: 1992/5/22

PubMed ID: 1379868

Journal name: Brain research (ISSN: 0006-8993)

ABSTRACT

The delayed neuronal death (DND) resulting from brief forebrain ischemia has recently been reported to be markedly attenuated by parenteral administration of the reversible protein synthesis inhibitor, anisomycin. Previous work suggests that ischemia-induced DND is mediated by glutamate acting at one or more glutamate receptors, since glutamate receptor antagonists have been reported to reduce ischemia-induced DND. Consequently, we tested whether anisomycin could modify DND induced by direct intracerebral administration of the excitotoxins, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxasole (AMPA) or kainic acid. Anisomycin, administered parenterally, in multiple doses did not alter DND induced by any of these excitotoxins, nor did combined parenteral and direct intracerebral injection of anisomycin protect against DND induced by AMPA. Thus, neurotoxicity induced by direct intracerebral administration of NMDA, AMPA or kainic acid does not appear to require de novo protein synthesis, and, therefore, is not likely to be mediated by the expression of a programmed cell death cascade.

Author List: Leppin C, Finiels-Marlier F, Crawley J N, Montpied P, Paul S M

Publication Types: Journal Article

Substances mentioned in the article: Glutamates; Receptors, Glutamate; Receptors, Neurotransmitter; Ibotenic Acid; N-Methylaspartate; Anisomycin; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Glutamate Decarboxylase; Kainic Acid;

Mesh terms: Animals; Anisomycin/pharmacology; Cell Death/drug effects; Glutamate Decarboxylase/drug effects; Glutamates; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; Male; N-Methylaspartate/pharmacology; Neurons/drug effects; Protein Biosynthesis; Rats; Rats, Inbred Strains; Receptors, Glutamate; Receptors, Neurotransmitter/drug effects; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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