In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of huntington disease

Mary Y. Heng, Peter J. Detloff, Phillip L. Wang, Joe Z. Tsien, Roger L. Albin

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N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is implicated as a proximate cause of neurodegeneration in Huntington Disease (HD). This hypothesis has not been tested rigorously in vivo. NMDAR-NR2B subunits are a major NR2 subunit expressed by striatal medium spiny neurons that degenerate in HD. To test the excitotoxic hypothesis, we crossed a well validated murine genetic model of HD (Hdh (CAG)150) with a transgenic line overexpressing NMDAR-NR2B subunits. In the resulting double-mutant line, we show exacerbation of selective striatal neuron degeneration. This is the first direct in vivo evidence of NR2B-NMDAR-mediated excitotoxicity in the context of HD. Our results are consistent with previous suggestions that direct and/or indirect interactions of mutant huntingtin with NMDARs are a proximate cause of neurodegeneration in HD.

Original languageEnglish (US)
Pages (from-to)3200-3205
Number of pages6
JournalJournal of Neuroscience
Issue number10
Publication statusPublished - Mar 11 2009


ASJC Scopus subject areas

  • Neuroscience(all)

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