| First Author | Zeron MM | Year | 2002 |
| Journal | Neuron | Volume | 33 |
| Issue | 6 | Pages | 849-60 |
| PubMed ID | 11906693 | Mgi Jnum | J:75438 |
| Mgi Id | MGI:2176630 | Doi | 10.1016/s0896-6273(02)00615-3 |
| Citation | Zeron MM, et al. (2002) Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron 33(6):849-60 |
| abstractText | Previous work suggests N-methyl-D-aspartate receptor (NMDAR) activation may be involved in degeneration of medium-sized spiny striatal neurons in Huntington's disease (HD). Here we show that these neurons are more vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice. Excitotoxic death of these neurons was increased after intrastriatal injection of quinolinate in vivo, and after NMDA but not AMPA exposure in culture. NMDA-induced cell death was abolished by an NR2B subtype-specific antagonist. In contrast, NMDAR-mediated death of cerebellar granule neurons was not enhanced, consistent with cell-type and NMDAR subtype specificity. Moreover, increased NMDA-evoked current amplitude and caspase-3 activity were observed in transgenic striatal neurons. Our data support a role for NR2B-subtype NMDAR activation as a trigger for selective neuronal degeneration in HD. |
