Figure 8.

Inhibition of NOX2-generated ROS protects dopaminergic neurons from SP/LPS- or SP/MPP⁺-induced synergistic neurotoxicity. Midbrain neuron-glia cultures were pretreated with 10⁻¹⁴ m DPI for 30 min before the addition of SP (10⁻¹⁴ m) and LPS or MPP⁺. Production of superoxide (A) and iROS (B) was accessed by measuring the SOD-inhibitable reduction of tetrazolium salt, WST-1 and increase of CM-H2-DCFDA, respectively (n = 5). The results of superoxide and iROS are expressed as a percentage of controls and above the control (mean ± SEM), respectively. The inhibitory effect of 10⁻¹⁴ m DPI on the synergistic dopaminergic neurodegeneration induced by SP and LPS (C) or MPP⁺ (D) was determined at 7 d of post-treatment by performing [³H]-DA uptake assay and THir neuron counts. E, Representative images confirmed the neuroprotection of dopaminergic neurons by DPI as shown by more THir neurons with longer and more abundant neurites compared with combined SP and LPS/MPP⁺ group (red arrowheads; n = 3). The results are expressed as a percentage of reduction of [³H]-DA uptake capacity or loss of THir cells (mean ± SEM, control group was considered as 0, no damage). Data were analyzed using one-way ANOVA, followed by Tukey's post hoc test. **p < 0.01. Scale bar, 50 μm.