PT  - JOURNAL ARTICLE
AU  - Heng, Mary Y.
AU  - Detloff, Peter J.
AU  - Wang, Phillip L.
AU  - Tsien, Joe Z.
AU  - Albin, Roger L.
TI  - <em>In Vivo</em> Evidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease
AID  - 10.1523/JNEUROSCI.5599-08.2009
DP  - 2009 Mar 11
TA  - The Journal of Neuroscience
PG  - 3200--3205
VI  - 29
IP  - 10
4099  - http://www.jneurosci.org/content/29/10/3200.short
4100  - http://www.jneurosci.org/content/29/10/3200.full
SO  - J. Neurosci.2009 Mar 11; 29
AB  - 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.