Fig. 3
αSyn-induced dopaminergic neurotoxicity is exacerbated by MC1R disruption and reversed by human MC1R transgene. MC1Re/e and WT mice were injected unilaterally with human WT αSyn AAV into the SN. A Contralateral and ipsilateral turns induced by amphetamine 12 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 12 mice/group. B Striatal dopamine content 16 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 12 mice/group. C TH staining and D stereological quantification of TH-positive and -negative cells in the SN 16 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 12 mice/group. Scale bar, 100 µm. MC1Re/eTg and MC1Re/e mice were injected unilaterally with human WT αSyn AAV into the SN. E Striatal dopamine content 16 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 6–7 mice/group. F TH staining and G stereological quantification of TH-positive and negative cells in the SN 16 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 6–7 mice/group. Scale bar, 100 µm. H p-αSyn staining and I quantification of p-αSyn aggregates in the ipsilateral SNpc 12 weeks post-AAV injection. Measurements were normalized by dividing values by the mean of the MC1Re/e mice and multiplying by 100. Two-tail Student’s t test. n = 4 mice/group. Scale bar, 50 µm. J Iba1 staining and morphological classification and K quantification of iba1-positive cells in the SNpc 12 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 4 mice/group. Scale bar, 30 µm. L Nrf2 and TH double-labeling and (M) quantification of nuclear and cytoplasmic Nrf2 in the SNpc 12 weeks post-AAV injection. Two-way ANOVA followed by Tukey’s post hoc test. n = 4 mice/group. Scale bar, 20 µm. N mRNA levels of Nrf2 target genes HO-1, NQO1, GCLC, and GCLM in the ipsilateral ventral midbrain 12 weeks post-AAV injection. Measurements were normalized by dividing values by the mean of the MC1Re/e mice. One-way ANOVA followed by Tukey’s post hoc test. n = 5 mice/group. *P < 0.05, **P < 0.01, ***P < 0.001