Figure 4

Expression of human aSyn induces the loss of neurons positive for dopaminergic markers in the SNpc of PGC1α-KO mice. PGC1α-KO mice or WT mice were injected in the SNpc with an AAV2/6 vector encoding aSyn or a non-coding vector (NCV). (a) At 3 months post-injection, there is no significant loss of TH-positive neurons in the SNpc (WT: n = 5 and PGC1α-KO: n = 10). (b) Overexpression of human aSyn is detectable by immunohistochemistry in nigral TH-positive neurons. Scale bar: 100 μm. (c) At 6 months post-injection, a significant loss of TH-positive neurons is observed in the SNpc of PGC1α-KO mice injected with AAV-aSyn. Statistical analysis: two-way ANOVA with Newman-Keuls post-hoc test; PGC1α-KO + aSyn: n = 18; PGC1α-KO + NCV: n = 5; WT + aSyn: n = 14; WT + NCV: n = 8; **p < 0.01, ***p < 0.001. (d) Analysis according to gender reveals that male PGC1α-KO mice are significantly more prone to aSyn-induced loss of TH neurons than female mice. Student’s t test: n = 9 for each gender; **p < 0.01. (e,f) Representative photomicrographs showing the loss of TH neurons in the AAV-aSyn injected hemisphere of PGC1α-KO mice (e), as compared to no loss in WT mice (f). The non-injected side (NInj) is shown for comparison. Scale bar: 100 μm.