Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: Unaltered vulnerability to excitotoxins and other insults

B. J. Snider, J. L. Moss, F. J. Revilla, C. S. Lee, V. C. Wheeler, M. E. Macdonald, D. W. Choi

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Glutamate-mediated excitotoxicity might contribute to the pathogenesis of Huntington's disease and other polyglutamine repeat disorders. We used murine neocortical cultures derived from transgenic and knock-in mice to test the effect of expression of expanded polyglutamine-containing huntingtin on neuronal vulnerability to excitotoxins or other insults. Neurons cultured from mice expressing either a normal length (HdhQ20) or expanded (HdhQ111) CAG repeat as a knock-in genetic alteration in exon one of the mouse Hdh gene [Hum Mol Genet 8 (1999) 115] had similar vulnerability to N-methyl-D-aspartate (NMDA) and kainate-mediated excitotoxicity. These neurons also exhibited similar vulnerability to oxidative stress (24 h exposure to 10-100 μM paraquat or 1-10 μM menadione), apoptosis (48 h exposure to 30-100 nM staurosporine or 1 μM dizocilpine maleate (MK-801) and proteasome inhibition (48 h exposure to 0.3-3 μM MG-132). Neocortical neurons cultured from mice transgenic for an expanded CAG repeat-containing exon 1 of the human HD gene (Mangiarini et al., 1996, R6/2 line) and non-transgenic littermate controls also had similar vulnerability to NMDA and kainate-mediated excitotoxicity. These observations suggest that expression of expanded polyglutamine-containing huntingtin does not acutely alter the vulnerability of cortical neurons to excitotoxic, oxidative or apoptotic insults.

Original languageEnglish
Pages (from-to)617-625
Number of pages9
JournalNeuroscience
Volume120
Issue number3
DOIs
StatePublished - Sep 1 2003

Keywords

  • Apoptosis
  • Huntington's disease
  • Oxidative stress
  • Polyglutamine
  • Proteasome

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