| First Author | Snider BJ | Year | 2003 |
| Journal | Neuroscience | Volume | 120 |
| Issue | 3 | Pages | 617-25 |
| PubMed ID | 12895502 | Mgi Jnum | J:128151 |
| Mgi Id | MGI:3766338 | Doi | 10.1016/s0306-4522(03)00382-8 |
| Citation | Snider BJ, et al. (2003) Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: unaltered vulnerability to excitotoxins and other insults. Neuroscience 120(3):617-25 |
| abstractText | Glutamate-mediated excitotoxicity might contribute to the pathogenesis of Huntington's disease and other polyglutamine repeat disorders. We used murine neocortical cultures derived from transgenic and knock-in mice to test the effect of expression of expanded polyglutamine-containing huntingtin on neuronal vulnerability to excitotoxins or other insults. Neurons cultured from mice expressing either a normal length (Hdh(Q20)) or expanded (Hdh(Q111)) CAG repeat as a knock-in genetic alteration in exon one of the mouse Hdh gene [Hum Mol Genet 8 (1999) 115] had similar vulnerability to N-methyl-D-aspartate (NMDA) and kainate-mediated excitotoxicity. These neurons also exhibited similar vulnerability to oxidative stress (24 h exposure to 10-100 microM paraquat or 1-10 microM menadione), apoptosis (48 h exposure to 30-100 nM staurosporine or 1 microM dizocilpine maleate (MK-801) and proteasome inhibition (48 h exposure to 0.3-3 microM MG-132). Neocortical neurons cultured from mice transgenic for an expanded CAG repeat-containing exon 1 of the human HD gene (Mangiarini et al., 1996, R6/2 line) and non-transgenic littermate controls also had similar vulnerability to NMDA and kainate-mediated excitotoxicity. These observations suggest that expression of expanded polyglutamine-containing huntingtin does not acutely alter the vulnerability of cortical neurons to excitotoxic, oxidative or apoptotic insults. |
