Figure 2. Dopamine-induced neurodegeneration of the SN is dependent on α-synuclein.
(a) At 5 mpi, fewer VMAT2-positive cells (arrows) were present in the SN of A53T TH-RREE mice compared with all other injection groups. Scale bar, 100 µm. (n = 3 mice per group). (b) Unbiased stereological counting of Nissl-positive neurons in the SN revealed a significant 25% loss of cells in A53T TH-RREE mice. The data are presented as mean ± s.e.m. (n = 3 mice per group except n = 4 mice for A53T TH-RREE, PA53T TH-RREE versus A53T CtrlVect = 0.0049, PA53T TH-RREE versus NonTg CtrlVect = 0.0316, PA53T TH-RREE versus NonTg TH-RREE = 0.0253, F(3,9) = 8.810; one-way ANOVA with Tukey’s correction for multiple comparisons). (c–d) Histological analysis of VMAT2 staining in the striatum, with subtraction of background staining in the cortex, indicated severe dopaminergic denervation in A53T TH-RREE mice. Scale bar, 200 µm. (n = 3 mice per group, PA53T TH-RREE versus A53T CtrlVect = 0.0043, PA53T TH-RREE versus NonTg CtrlVect = 0.0163, PA53T TH-RREE versus NonTg TH-RREE = 0.0163, F(3,8) = 10.02; one-way ANOVA with Tukey’s correction for multiple comparisons). (e–f) Striatal DAT levels normalized to the actin loading control were increased in NonTg TH-RREE mice relative to NonTg CtrlVect, whereas DAT levels were decreased in A53T TH-RREE mice as compared to A53T CtrlVect. Blots are cropped; for full-length blots see Supplementary Fig. 11. (n = 3 mice per group except n = 4 mice for NonTg CtrlVect, PA53T TH-RREE versus A53T CtrlVect = 0.0211, PA53T CtrlVect versus NonTg CtrlVect = 0.0097, PNonTg TH-RREE versus NonTg CtrlVect = 0.0466, F(3,9) = 8.411; one-way ANOVA with Tukey’s correction for multiple comparisons). Box plots show median, 25th and 75th percentiles, minimum and maximum values. *P < 0.05, **P < 0.01.