Quinolinate and kainate neurotoxicity in neostriatal cultures is potentiated by co-culturing with neocortical neurons

E. Galarraga, D. J. Surmeier*, S. T. Kitai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

It has been suggested that a disorder in the regulation of excitatory amino acids (EAA) may underlie the loss of neostriatal neurons seen in Huntington's disease. The role of neocortical afferent fibers in determining the EAA sensitivity of neostriatal neurons was assessed by comparing EAA toxicity in co-cultures of neocortex and neostratum with that of neostriatum alone. In culturesalone, EAAs produced only modest neuronal losses. Kainate, which tended to be the most potent excitotoxin, produced a loss of approximately 30% of the neurons after a 5-min exposure at a 1-mM concentration. In co-cultures, the sensitivity of neostriatal neurons to EAA toxicity was dramatically enhanced; toxicity was increased about two-fold for kainate and quinolinate at millimolar concentrations and as much as 8-fold for quinolinate at micromolar concentrations. The effects of EAA co-incubation with theN-methyl-d-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid, suggested that the toxic actions of quinolinate, but not kainate, were mediated largely by NMDA receptors.

Original languageEnglish (US)
Pages (from-to)269-276
Number of pages8
JournalBrain research
Volume512
Issue number2
DOIs
StatePublished - Apr 2 1990

Keywords

  • Excitatory amino acid
  • Glutamate
  • Neocortex
  • Neostriatum
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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