Fig. 5: TfR2-targeted deletion is partially protective against alpha-synuclein pre-formed fibrils (PFF) intracranial seeding.

A Schematic of the stereotactic injection procedure during which PFF have been injected in the right striatum. B TfR2 deletion provides protection against striatal denervation induced by PFF, as indicated by TH immunohistochemistry. C Unbiased stereological counts of dopaminergic neurons in the SNpc indicate that TfR2-targeted deletion is protective against PFF-induced degeneration in females, but not in males. D Perls’ staining for Fe3+ did not reveal any effect of TfR2 deletion on iron accumulation in the SNpc induced by PFF (left panel). Immunodetection of TH-positive neurons combined with Perls’ staining reveals iron deposits also in SNpc dopamine neurons (right panel). E Increased levels of ser129 p-α-synuclein in the substantia nigra (arrows) confirms α-synuclein stress in PFF-injected animals that is not ameliorated by TfR2 deletion (green signal). Graphs represent scatter plots with bars. Two-tailed t test; *p < 0.05, **p < 0.005, ***p < 0.001. Calibration bars: 1 mm in (B), 2 mm (left panel) and 50 μm (right panel) in (D), and 50 μm in (E).