| First Author | Shehadeh J | Year | 2006 |
| Journal | Neurobiol Dis | Volume | 21 |
| Issue | 2 | Pages | 392-403 |
| PubMed ID | 16165367 | Mgi Jnum | J:105728 |
| Mgi Id | MGI:3616384 | Doi | 10.1016/j.nbd.2005.08.001 |
| Citation | Shehadeh J, et al. (2006) Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease. Neurobiol Dis 21(2):392-403 |
| abstractText | Huntington disease (HD), caused by expansion >35 of a polyglutamine tract in huntingtin, results in degeneration of striatal medium spiny neurons (MSNs). Previous studies demonstrated mitochondrial dysfunction, altered intracellular calcium release, and enhanced NMDAR-mediated current and apoptosis in cellular and mouse models of HD. Here, we exposed cultured MSNs from YAC transgenic mice, expressing full-length human huntingtin with 18, 72, or 128 repeats, to a variety of apoptosis-inducing compounds that inhibit mitochondrial function or increase intracellular calcium, and assessed apoptosis 24 h later. All compounds produced a polyglutamine length-dependent increase in apoptosis, but NMDA produced the largest potentiation in apoptosis of YAC72 and YAC128 versus YAC18 MSNs. Moreover, reduction of NMDAR-mediated current and calcium influx in YAC72 MSNs to levels seen in wild-type reduced NMDAR-mediated apoptosis proportionately to wild-type levels. Our results suggest that increased NMDAR signaling plays a major role in enhanced excitotoxic MSN death in this HD mouse model. |
