The mitochondrial inhibitor malonate enhances NMDA toxicity in the neonatal rat striatum.
Intra-striatal injections of the mitochondrial inhibitor malonate elicit age-dependent neuronal damage in rat brain; injury is more extensive in older animals than in young adults. We investigated the neurotoxic potential of malonate in the immature rat brain. We found that 7-day-old (P7) rats were highly resistant to malonate neurotoxicity. Yet, although intra-striatal injections of 1 mumol malonate did not elicit overt tissue injury in P7 rats, co-administration of this dose of malonate with a dose of NMDA close to its toxicity threshold (2.5 nmol) doubled the severity of resulting excitotoxic injury.
D000818:Animals; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006651:Histocytochemistry; D008314:Malonates / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects*; D016202:N-Methylaspartate / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018690:Excitatory Amino Acid Agonists; D008314:Malonates; D016202:N-Methylaspartate; C030290:malonic acid