Fig. 2. Seeded α-Syn pathology leads to progressive DA system degeneration.
(A–D) pSyn immunostaining in SNpc of mice sacrificed at 30d, 90d, or 180d following striatal PFF injection. (A) Diffuse perinuclear pSyn inclusions (black arrowheads) at 30d post-injection. (B,C) Dense LB-like inclusions (black arrows) at 90d and 180d post-injection. Absence of pSyn pathology in SNpc contralateral to the PFF injection site (D) and in ipsilateral SNpc of PBS-injected mouse (E) at 180d. (F–I) TH-immunostaining of SNpc at 30d, 90d and 180d following inoculation with Syn PFFs. Arrowheads in (G) indicate neurons with reduced TH staining in the ipsilateral SNpc at 90d post-injection. (H,I) Ventral SNpc, ipsilateral and contralateral to the site of PFF injection at 180d. Arrows point to DA neuron loss. (J) PBS-injected control at 180d post-injection. (K) Percentage of SNpc TH-neurons containing pSyn-immunoreactive inclusions for each treatment group. Data for treated ipsilateral (black) and contralateral (grey) hemispheres are shown. #p<0.001 paired t-test (N = 3–5 animals per group). (L,M) Quantification of TH-immunoreactive neurons in the SNpc and VTA of mice after intrastriatal PFF-, monomer- or PBS-injection. Data represent mean number of cells per region +/− SEM (N = 3–4 animals per group). *P<0.05 one-way ANOVA. Scale bars: 25 μm (A–D);50 μm (E–J).
