Fig. 1

Experimental design and PFF quality control. a Experimental design: 2-month-old male Fischer344 rats (N = 114) received two unilateral intrastriatal injections of either sonicated α-syn PFFs, Dulbecco’s PBS (PBS), or rat serum albumin (RSA; follow-up study only). Cohorts of rats were euthanized at an early time point (2 weeks) and monthly intervals thereafter. Brains were removed and processed for immunohistochemical measures of pathology as detailed. b Electron micrographs of unsonicated (left) α-syn PFFs and sonicated α-syn PFFs (right); scale bars = 100 nm. c Measurement distribution of ~ 500 sonicated PFFs prior to injection; mean fibril size = 51.22 ± 1.31 nm. d Schematic of PFF model of synucleinopathy. Sonicated α-syn fibrils are injected into the striatum and taken up by nigrostriatal terminals (1), after which they template and convert endogenous α-syn to a hyperphosphorylated, pathological form (2), ultimately accumulating into Lewy neurite- and Lewy body-like inclusions (3). Abbreviations: α-syn = alpha-synuclein; PFFs = pre-formed alpha-synuclein fibrils; PBS = phosphate-buffered saline; DMS = dorsal medial striatum; VLS = ventrolateral striatum; IHC = immunohistochemistry; pSyn = α-syn phosphorylated at serine 129; MHC-II = major histocompatibility complex-II; Iba-1 = ionized calcium-binding adaptor molecule 1; TH = tyrosine hydroxylase; NeuN = neuronal nuclei; CD68 = cluster of differentiation 68; QC = quality control