1-Aminocyclopropane-carboxylic acid reduces NMDA-induced hippocampal neurodegeneration in vivo.
The effect of systemic treatment with 1-aminocyclopro-panecarboxylic acid (ACPC), a partial agonist at the glycine site of the NMDA receptor, on convulsions and neurodegeneration induced by intrahippocampal injection of NMDA was investigated in mice. Five days after intrahippocampal NMDA infusion, 80-100% pyramidal cell death was observed in the CA1 region of the hippocampus. Pretreatment with ACPC prevented the lethal effects of NMDA and significantly reduced seizure induction. ACPC reduced cell death to 40% of that induced by a dose of NMDA (6 nmol) that damaged 80% of hippocampal CA1 neurones in untreated animals. These findings provide further evidence that ACPC can reduce NMDA receptor function in vivo and suggest that partial agonists at the glycine site of the NMDA receptor complex may be useful anticonvulsant and neuroprotective agents.
Zapata
A
A
Unitat de Neurobiologia, CID, CSIC, Barcelona, Spain.
Capdevila
J L
JL
Viu
E
E
Trullas
R
R
D000596:Amino Acids / Q000494:pharmacology*; D000598:Amino Acids, Cyclic; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012640:Seizures / Q000139:chemically induced / Q000473:pathology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; C023863:1-aminocyclopropane-1-carboxylic acid; D016202:N-Methylaspartate