Fig. 2

Induction of αSyn pathology following injection of αSyn fibrils in the IC of line M20 mice. 2 month old Line M20 mice were injected with pre-formed human WT αSyn fibrils in IC (a, Cohort 1) or mouse WT αSyn fibrils in IC (b, Cohort 2) or human WT αSyn fibrils in the CPu (c, Cohort 3) and analyzed after 4 months. Abundant αSyn inclusion pathology, detected by pSer129-αSyn antibodies (81A and EP1536Y) was observed in most areas of the brain, even those that are not directly connected to the striatum, such as the hippocampus. Surprisingly, areas adjacent to the IC, such as the ventral and dorsal striatum had few pathological inclusions. Inclusion pathology was confirmed using a conformation-specific antibody against αSyn, Syn506, and p62/Sqstm1 antibody, which is a well-established marker of cytoplasmic LB inclusions. Both perikaryal (arrowhead) and neuritic (arrow) αSyn pathology were observed. The relative distribution and abundance of αSyn pathology in Cohort 3 was similar to Cohort 1, except that mice in Cohort 3 had relatively higher density of αSyn inclusion pathology in the striatum. Note that since 1 mouse in Cohort 2 died prematurely from hindlimb paralysis, neuropathological analysis could not be performed. Scale Bar, 100 μm; n = 3–5 mice