Figure 2

rAAV2/7 vector-mediated overexpression of α-synuclein in mouse SN induces progressive cell loss and α-synuclein aggregation. (A) Images of immunohistochemical stainings for α-synuclein showing the whole area of transduction 5 days after rAAV2/7-α-synuclein injection. Scale bar = 500 μm. (B) Overexpression of WT α-synuclein induces a progressive and dose-dependent α-synuclein-positive cell loss over time in the injected SN. Absence of immunoreactivity in the contralateral SN at 5 days after injection when expression was maximal. Right panels are magnifications of the overview (left panels). Scale bars = 200 μm. N-inj: non-injected side. (C) High magnification pictures demonstrate the presence of α-synuclein-positive aggregates (arrows) in the SN for each vector dose at 4 weeks post-injection. (D) High magnification picture of an α-synuclein-positive cell without aggregates. Scale bars (C-D) = 5 μm. (E) Stereological quantification of the α-synuclein-positive volume in the SN of mice injected with 3 different WT α-synuclein vector doses and a unique A53T α-synuclein vector dose after 5 days, 4 weeks and 8 weeks. (F) Stereological quantification of the number of α-synuclein-positive cells in the SN of mice after 5 days, 4 weeks and 8 weeks. Asterisks (*) depict significant decrease respective to 4 weeks, unless specified otherwise. 5 days 4,0E + 11 GC/ml WT/A53T: n = 3; 5 days 2,6/8,0E + 11 GC/ml WT: n = 4; 4 weeks: n = 4; 8 weeks: n = 4.