| First Author | Heng MY | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 10 | Pages | 3200-5 |
| PubMed ID | 19279257 | Mgi Jnum | J:147069 |
| Mgi Id | MGI:3839189 | Doi | 10.1523/JNEUROSCI.5599-08.2009 |
| Citation | Heng MY, et al. (2009) In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of Huntington disease. J Neurosci 29(10):3200-5 |
| abstractText | 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. |
