Fig. 4.

Striatal dopaminergic deficit in MI2 mice. a DA was measured in striatal lysates of MI2 and C57Bl/6S mice at 3, 6 and 12 months of age (mean ± SEM, n = 5–8 mice per group). A main effect of age and interaction between genotype and age was identified by two-way ANOVA with Bonferroni correction, showing a significant reduction of DA levels in MI2 mice at 12 months compared to 12 month old C57Bl/6S mice, and to 3 month old and 6 month old MI2 mice (*p < 0.05, ***p < 0.001) (see also Supplementary Fig. S5a, Online Resource 1 and for DDPAC content S5c). b Striatal DA release was measured by in vivo microdialysis following the infusion of 50 mM KCl for 60 min between 40 and 100 min of the experiment. Data are expressed as a fold difference compared to the baseline fraction (0 min), normalized to the value obtained in age-matched C57Bl/6S controls at 60 min (mean ± SEM, n = 4–6 mice). At 3 months of age no difference between MI2 and C57Bl/6S mice was observed, but a significant progressive decrease in DA release was found at 6, 9 and 12 months of age in MI2 compared with C57Bl/6S mice (see also Supplementary Fig. S5b, Online Resource 1). Two-way mixed ANOVA revealed a significant interaction between genotype and sample time at 6, 9 and 12 months of age (*p < 0.05, **p < 0.01, t test for individual sampling time points) (see detailed statistical evaluation in Online Resource)