Figure 1.. α-syn PFF injection into the gut triggers progressive spreading of α-syn pathology to…
Figure 1.. α-syn PFF injection into the gut triggers progressive spreading of α-syn pathology to the enteric nervous system followed by spread to connected brain regions.
(A) Overview of the site of injection and vagotomy (B) Representative double-immunostaining for pSer129-α-syn (white) and Tuj-1 (red) in the upper duodenum (UD) and pyloric stomach (PS) after 1 month post-injection. (C) Quantification of pSer129-α-syn positive neurons normalized to Tuj-1 positive neurons in the upper duodenum and pyloric stomach (n=4). (D) Brain distribution of pSer129-α-syn accumulation in mice that received α-syn PFF in the gut. pSer129-α-syn immunohistochemistry from the dorsal motor nucleus of the vagus to the olfactory bulb of α-syn PFF gastrointestinal injected mice sacrificed at 1, 3, 7, and 10 months post-injection. (E) Quantification of pSer129-α-syn immunoreactivity shown in panel D (n=4). (F) Diagram illustrating the CNS distribution of pSer129-α-syn representing α-syn pathology (red dots) in the brain from coronal sections from 1, 3, 7, and 10 months post-injection. Error bars represent the mean ± S.E.M. Statistical significance was determined using a two-way ANOVA followed by post-hoc Bonferroni test for multiple group comparison. ***P < 0.001. N.D: not detected. BLA, basolateral amygdala; CPu, upper caudate-putamen; Ctx, cortex; DG, dentate gyrus; DMV, dorsal motor nucleus of the vagus; HIP, hippocampus; LC, locus coeruleus; MO, medulla oblongata; OB, olfactory bulb; PFC, prefrontal cortex; PS, pyloric stomach; SNc. substantia nigra pars compacta; SNr, substantia nigra pars reticulate; STR, striatum; UD, upper duodenum. See also Figures S1, S2 and S3.