The mitochondrial inhibitor malonate enhances NMDA toxicity in the neonatal rat striatum

Brain Res Dev Brain Res. 1995 Aug 28;88(1):117-21. doi: 10.1016/0165-3806(95)00085-r.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Synergism
  • Excitatory Amino Acid Agonists / toxicity*
  • Histocytochemistry
  • Malonates / toxicity*
  • Mitochondria / drug effects*
  • N-Methylaspartate / toxicity*
  • Neostriatum / drug effects*
  • Neostriatum / growth & development
  • Neostriatum / pathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Excitatory Amino Acid Agonists
  • Malonates
  • N-Methylaspartate
  • malonic acid