Fig. 4

MC1R agonists protect against αSyn-induced dopaminergic neurotoxicity. C57Bl/6 J mice were injected with αSyn or empty vector (Vec) AAV, treated subcutaneously with 20 mg/kg BMS-470539 (BMS-) or saline for 4 weeks, and sacrificed 16 weeks post-AAV injection. A Striatal dopamine content. Two-way ANOVA followed by Tukey’s post hoc test. n = 6–8 mice/group. B Stereological quantification of TH-positive cells in the SN. Two-way ANOVA followed by Tukey’s post hoc test. n = 6–8 mice/group. C p-αSyn staining and D quantification of p-αSyn aggregates in the ipsilateral SN. Measurements were normalized by dividing values by the mean of the vehicle-treated group and multiplying by 100. Two-tailed Student’s t test. n = 4 mice/group. Scale bar, 50 µm. WT and MC1R^e/e mice were injected unilaterally with 3 nmol NDP-MSH into the striatum and then with αSyn AAV into the SN. Mice were sacrificed 16 weeks post-AAV injection. E Contralateral and ipsilateral turns induced by amphetamine 12 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 7 mice/group. F Striatal dopamine content. Two-way ANOVA followed by Tukey’s post hoc test. n = 7 mice/group. G Stereological quantification of TH-positive cells in the SN. Two-way ANOVA followed by Tukey’s post hoc test. n = 7 mice/group. H p-αSyn staining and I quantification of p-αSyn aggregates in the ipsilateral SN. Measurements were normalized by dividing values by the mean of the vehicle-treated group and multiplying by 100. Two-tail Student’s t test. n = 4 mice/group. Scale bar, 50 µm. J Morphological classification and quantification of iba1-positive cells in the SN in WT mice. Two-way ANOVA followed by Tukey’s post hoc test. n = 4 mice/group. K Nuclear and cytoplasmic Nrf2 ratio in the SN in WT mice. Two-way ANOVA followed by Tukey’s post hoc test. n = 4 mice/group. *P < 0.05, **P < 0.01, ***P < 0.001