Systematic gait analysis in alpha-synuclein transgenic line 62 mice using the CatWalk

Abstract

The aggregation of α-synuclein in the brain is a characteristic hallmark of Parkinson’s disease (PD), a neurodegenerative disorder with distinct motor and gait abnormalities. The recapitulation of gait assessment in rodents is therefore a useful tool to determine gait impairments in pre-clinical disease models of PD. The CatWalk automated gait analyses system was used to systematically access gait performance in line 62 (L62) transgenic mice. L62 mice express full-length human α-synuclein fused with a signal sequence peptide as a pre-clinical mouse model for PD and related synucleinopathies. For both genotypes, male mice spent less time running, had a significantly lower average speed, smaller base of support (BOS) and stride lengths compared to female mice. L62 transgenic mice (male and female) ran less, had a smaller hind BOS, and showed spatial and temporal interlimb coordination deficiencies compared to WT mice. Additionally, 12-month old mice ran less time compared to 6-month old mice, and the spatial and temporal deficits in L62 were most pronounced in 12 month old male mice. CatWalk gait performance of α-synuclein transgenic L62 mice was impaired and more pronounced in aged mice. Kinetic and coordination-related gait parameters were affected similarly in male and female L62, and these changes appeared already by 6 months. Lastly, spatial deficits emerged earlier in male L62 while temporal deficits emerged earlier in female L62 mice.