| First Author | Cao JK | Year | 2019 |
| Journal | Neurobiol Dis | Volume | 132 |
| Pages | 104607 | PubMed ID | 31499139 |
| Mgi Jnum | J:282567 | Mgi Id | MGI:6381696 |
| Doi | 10.1016/j.nbd.2019.104607 | Citation | Cao JK, et al. (2019) Sex-dependent impaired locomotion and motor coordination in the HdhQ200/200 mouse model of Huntington's Disease. Neurobiol Dis 132:104607 |
| abstractText | Huntington's Disease (HD) is a fatal neurodegenerative disease characterized by severe loss of medium spiny neuron (MSN) function and striatal-dependent behaviors. We report that female HdhQ200/200 mice display an earlier onset and more robust deterioration in spontaneous locomotion and motor coordination measured at 8months of age compared to male HdhQ200/200 mice. Remarkably, HdhQ200/200 mice of both sexes exhibit comparable impaired spontaneous locomotion and motor coordination at 10months of age and reach moribund stage by 12months of age, demonstrating reduced life span in this model system. Histopathological analysis revealed enhanced mutant huntingtin protein aggregation in male HdhQ200/200 striatal tissue at 8months of age compared to female HdhQ200/200. Functional analysis of calcium dynamics in MSNs of female HdhQ200/200 mice using GCaMP6m imaging revealed elevated responses to excitatory cortical-striatal stimulation suggesting increased MSN excitability. Although there was no down-regulation of the expression of common HD biomarkers (DARPP-32, enkephalin and CB1R), we measured a sex-dependent reduction of the astrocytic glutamate transporter, GLT-1, in female HdhQ200/200 mice that was not detected in male HdhQ200/200 mice when compared to respective wild-type littermates. Our study outlines a sex-dependent rapid deterioration of striatal-dependent behaviors occurring in the HdhQ200/200 mouse line that does not involve alterations in the expression of common HD biomarkers and yet includes impaired MSN function. |
