Fig. 2

Dopaminergic neurodegeneration induced by human D620N VPS35 expression in mice occurs independent of endogenous αSyn. A) Immunofluorescent co-localization of human VPS35 (V5) with TH-positive neurons in the ipsilateral substantia nigra of WT or SNCA KO mice at 12 weeks following the injection of AAV2/6 vectors (control MCS or D620N VPS35). B) Immunohistochemical staining of nigral TH-positive neurons at 12 weeks after unilateral intranigral injection of MCS or D620N VPS35 vectors. C) Stereological quantitation of nigral TH-positive dopaminergic and total Nissl-positive neuronal loss in WT and SNCA KO mice induced by D620N VPS35 or control virus at 12 weeks. Data are expressed as percent neuronal loss relative to the uninjected nigra, with bars representing the mean ± SEM, n = 9–12 mice/group. ***P < 0.001 or ****P < 0.0001 by one-way ANOVA with Tukey’s multiple comparison test, as indicated. D) Representative photomicrographs of immunostaining for TH-positive nerve terminals in the striatum at 12 weeks following AAV vector delivery. E) Quantitation of striatal TH-positive fibers by optical density. Data are expressed as percent loss of TH-positive fibers relative to the uninjected side, with bars representing the mean ± SEM, n = 9–12 mice/group. n.s., non-significant by one-way ANOVA with Tukey’s multiple comparison test