Figure 3

α-Synuclein overexpression leads to progressive dose-dependent dopaminergic cell death in mouse SN and STR. (A-B) Immunohistochemical stainings for TH in the (A) SN and in the (B) STR of mice injected with 3 different WT α-synuclein vector doses and a unique eGFP or A53T α-synuclein vector dose show that overexpression of α-synuclein induces a progressive and dose-dependent TH cell loss over time. Overexpression of A53T α-synuclein triggers a comparable loss to WT α-synuclein at the same vector dose. Note the absence of dopaminergic neurodegeneration in the contralateral side at 8 weeks post-injection when cell loss was maximal. Scale bar (A) = 250 μm and (B) = 500 μm. N-inj: non-injected side. (C-D) Stereological quantification of the number of TH-positive neurons in the SN of the (C) injected side and (D) non-injected side after 5 days, 4 weeks and 8 weeks. (E) Stereological quantification of the TH-positive volume in the STR of the injected side at 5 days, 4 weeks and 8 weeks post-injection. Asterisks (*) represent significant decrease respective to eGFP, unless specified otherwise. Dagger (‡) depicts significant decrease respective to 4,0E + 11 GC/ml WT/A53T. 5 days 8,0E + 11 GC/ml eGFP and 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.