Fig. 3
Progressive motor deficits in MSA mice during aging. The performance of the PLP-α-syn and control mice at the pole test is measured by the T-turn time (a) and the T-total time (b). Two-way ANOVA shows a significant effect of both genotype and aging in pole test (T-turn: effect of genotype F1,58 = 24.21, p < 0.0001, effect of age F3,58 = 6.192, p = 0.001, interaction F3,58 = 8.093, p = 0.0001; T-total: effect of genotype F1,54 = 1.097, p = 0.2996, effect of age F3,54 = 2.895, p = 0.0435, interaction F3,54 = 6.781, p = 0.0002). Post hoc Bonferroni correction shows increase of the T-turn and the T-total time in PLP-α-syn mice at 12 and 18 months of age, with respect to the control mice. Similarly, age- and genotype-related motor function deterioration is observed with the beam test, by measuring the time to go across the beam (c) and the number of slips (d). Two-way ANOVA shows a significant effect of both genotype and aging in the beam test (crossing time: effect of genotype F1,65 = 6.913, p = 0.0107, effect of age F3,65 = 24.96, p < 0.0001, interaction F3,65 = 17.89, p < 0.0001; number of slips: effect of genotype F1,64 = 37.67, p < 0.0001, effect of age F3,64 = 33.3, p < 0.0001, interaction F3,64 = 17.87, p < 0.0001). Post hoc Bonferroni correction shows that the transgenic animals need significantly more time and make significantly more slips than the wild-type controls at 12 and 18 months of age. Gait analysis focused on stride length (e) and stride length variability (expressed in cm (f) and as a coefficient of variability in percentage (g)). A tendency towards shorter stride length is seen in the PLP-α-syn mice compared to the controls (two-way ANOVA with factors genotype and age: effect of genotype F1,55 = 9.477, p < 0.01, effect of age F3,55 = 2.056, p > 0.05, interaction F3,55 = 0.0517, p > 0.05), but sub-group differences are not significant after post-hoc Bonferroni test. Two-way ANOVA shows a significant effect of aging on stride length variability (absolute in cm: effect of genotype F1,55 = 0.0254, p = 0.8783, effect of age F3,55 = 4.304, p = 0.0083, interaction F3,55 = 5.375, p = 0.0025; CV%: effect of genotype F1,56 = 1.3, p = 0.259, effect of age F3,56 = 5.841, p = 0.0015, interaction F3,56 = 6.161, p = 0.0011). Post hoc Bonferroni correction shows that the stride length variability in PLP-α-syn mice is significantly higher than in the controls at 18 months. h Grip strength decreases in both control and transgenic animals between 2 and 12 months of age, and in the latter ones this decrement continues till 18 months of age. Two-way ANOVA shows a significant effect of aging and genotype on the hanging time, but no interaction between the factors (effect of genotype F1,66 = 20.09, p < 0.0001, effect of age F3,66 = 8.09, p < 0.0001, interaction F3,66 = 1.456, p = 0.2345). Post hoc Bonferroni correction shows that the grip strength in the MSA mice at 18 months of age is significantly lower than in the wild-type animals. ** p < 0.01, ***p < 0.001 versus age-matched controls; # p < 0.05, ## p < 0.01, ### p < 0.001; for all groups n = 7–11