Fig. 1. 10-NO₂-OA activates Nrf2 regulating heme oxygenase-1 expression in dopaminergic neurons of the SNpc.

a Immunohistochemical assay for Nrf2 (Cohort 2, n = 4) reveals a significant nuclear recruitment of Nrf2 in DA neurons both in rats treated with 10-NO₂-OA (45 mg/Kg) and Rotenone + 10-NO₂-OA. A remarkable increase of Nfr2 expression in nigrostriatal DA neurons was also observed in 10-NO₂-OA treatments, whereas rotenone induced downregulation of Nrf2 (Scale bar: 20 μm). b (upper graphic) Quantification of nuclear Nrf2. Symbols represent the percent of the ratio nuclear/total Nrf2 from a single animal (3 slices /brain). Statistical analysis was performed by one-way ANOVA with post hoc Bonferroni correction (*p < 0.0001 compared to Vehicle and Rotenone). b (lower graphic) Quantification of Nrf2 fluorescence intensity. Symbols represent the normalized means of the intensity (with Vehicle set at 100%) from a single rat (3 slices /brain). Statistical analysis was performed by one-way ANOVA with post hoc Bonferroni correction (*p < 0.0001 compared to Vehicle, #p < 0.0001 compared to 10-NO₂-OA and Rotenone + 10-NO₂-OA). c Immunohistochemical stain for HO-1 expression (Cohort 2). Rats treated with 10-NO₂-OA (45 mg/Kg) or co-treated with 10-NO₂-OA and rotenone displayed a significant increase of HO-1 protein expression (red) in dopaminergic nigrostriatal neurons (TH, blue—Scale bar: 35 μm). d Quantification of HO-1 fluorescence intensity. Symbols represent the normalized means of the intensity (with Vehicle set at 100) from a single rat (6 slices/brain). Statistical analysis was performed by one-way ANOVA with post hoc Bonferroni correction (*p < 0.0001 compared to Vehicle and Rotenone).