RT Journal Article
SR Electronic
T1 <em>In Vivo</em> Evidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3200
OP 3205
DO 10.1523/JNEUROSCI.5599-08.2009
VO 29
IS 10
A1 Heng, Mary Y.
A1 Detloff, Peter J.
A1 Wang, Phillip L.
A1 Tsien, Joe Z.
A1 Albin, Roger L.
YR 2009
UL http://www.jneurosci.org/content/29/10/3200.abstract
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.