Fig. 5

Peripherally injected PFF induces small- and medium-sized myelinated fiber pathology in the dorsal roots. a Morphological evaluation of the dorsal sensory roots by EM. Representative low magnification images of the sensory roots from vehicle- (panel i, PBS, pH 7.4), monomeric α-Syn (panel ii) and α-Syn PFF-injected mice (panel iii), denoting normal distribution of myelinated fibers with some morphological abnormalities identified in the PFF cohort (panel iii, white arrows). Scale bar 20 μm. Panels iv–ix denote high magnification pictures (scale bar = 2 µm), and respective insets (scale bar = 250 nm), showing an abnormal structure of the Remak bundles composed of numerous unmyelinated axons enclosed by basement membrane of Schwann cells, particularly in the monomeric and PFF- injected mice (panel vi–ix). Note electron loose Schwann cell processes, and the lack of these processes around some of the axons (orange arrows). b Image displaying completely (panel i) or partially demyelinated axon (panel ii) (> 1.5 μm diameter; white asterisks). In Panel (i), flat sheets of Schwann cell cytoplasmic processes enclosed by a common basement membrane, designated as bands of Büngner (black arrow) that are usually formed after degeneration of unmyelinated axons, can also be observed. Panel (iii) Picture showing degeneration of small- and medium-sized myelinated fibers (blue arrows), Schwann cell cytoplasm containing degradation products and myelin ovoids (red arrowhead), free debris in the endoneurium (orange arrow) and disorganized Remak bundles with few unmyelinated C-fibers (pink arrow). Panel (iv) A macrophage engulfing myelin fragments is highlighted. Panel (v) Green arrows feature projection of endothelial cell nuclei into the lumen of blood vessels. Panel (vi) Exhibits an endothelial cell with abnormal morphology, with irregular small branches and swollen electron loose cytoplasm (yellow arrow). Scale bars are 2 μm (Panels i, vi) and 5 μm (Panels ii, iii, iv, v). c Dorsal sensory roots semi-quantitative pathology scoring summary of the three cohorts in this study; the number of mice with detectable pathological abnormalities in C-fibers, blood vessels, Schwan cells or axonal degeneration and demyelination in the endoneurium (n/6 for vehicle- injected mice and n/8 for both monomeric α-Syn- and PFF-injected mice) is shown along with density of pathology represented by colour where darker colour indicates aggravated pathology