Temporal and Spatial Dynamics of Motor Dysfunction in Preclinical Parkinson's Disease and Aging

Gait assessments have been performed in several murine models of Parkinson's Disease (PD), but the M83^+/- mouse model of PD has been relatively understudied in this context. Metrics of gait swing, stride length and frequency, and ataxia were collected in M83^+/- mice with peripheral injections of α-syn preformed fibrils (PFF) and in aged M83^+/- mice without fibrils using the DigiGait^™ system. PFF-mice showed significantly decreased swing in all limbs (0.11 ± 0.02 vs. 0.13 ± 0.03, p = 0.007) compared to age-matched controls. Stride frequency was significantly increased in all limbs (3.9 ± 0.4 vs. 3.0 ± 0.5, p = 0.010) of PFF-treated mice. Swing was significantly greater in the hindlimbs of young M83^+/-+PFF mice compared to aged M83^+/- mice (0.11(0.5) vs. 0.08 (0.3), p = 0.015). Ataxia was significantly higher in young M83^+/-+PFF mice compared to control for forelimbs (1.1 ± 1.0 vs. 0.6 ± 0.5, p = 0.027), hindlimbs (0.9 ± 1.0 vs. 0.3 ± 0.2, p = 0.016), and all limbs (1.0 ± 1.0 vs. 0.3 ± 0.5, p = 0.015). M83^+/- mice demonstrate significant gait abnormalities consistent with features of PD. This study supports the utility of the M83^+/- murine model for preclinical gait analyses in PD.