Failure of a protein synthesis inhibitor to modify glutamate receptor-mediated neurotoxicity in vivo.
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.
Leppin
C
C
Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892.
Finiels-Marlier
F
F
Crawley
J N
JN
Montpied
P
P
Paul
S M
SM
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000187:drug effects; D005971:Glutamates; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D000841:Anisomycin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005968:Glutamate Decarboxylase; D007608:Kainic Acid