Fig. 2: ME injection of PD-extracts triggers αS pathology along the gut–brain axis.

a,b, αS s129p⁺ pathology in duodenal myenteric plexus at 1 month (a) and 3 months (b) post-NHC-αS versus PD-αS injection. c, Quantification of αS-GFP^high cells per mm² at 1 month and 3 months postinjection. n = 6 for αS-NHC, 1 month; n = 8 for αS-PD, 1 month; n = 5 for αS-NHC and αS-PD, 3 months. Two experiments. d, Quantification of αS s129p⁺ pathology at 1 month and 3 months postinjection. One datapoint, average of 1 mouse, 5–9 ROIs per mouse. n = 6 mice for αS-NHC, 1 month; n = 8 for αS-PD, 1 month; n = 5 mice for αS-NHC and n = 6 mice for αS-PD, 3 months. Two experiments. e, Gastrointestinal transit time at 1 month and 3 months postinjection. n = 7 mice for αS-NHC, n = 6 mice for αS-PD, 1 month; n = 7 mice for αS-NHC, n = 5 mice for αS-PD, 3 months. Two experiments, data analysed using two-way ANOVA (c–e) with Bonferroni’s multiple-comparison test (d). f, Widefield images of s129p⁺ αS pathology in brainstem at 3 months postinjection, blue arrows highlight αS inclusions. g, Quantification of s129p⁺ αS pathology in brainstem at 1 month and 3 months postinjection, n = 4 mice for αS-NHC, 1 month and n = 5 mice for αS-NHC, 3 months; αS-PD, 1 month and 3 months. Two experiments, two-way ANOVA with Bonferroni’s multiple-comparison test. h, αS s129p⁺ pathology in SNpc at 3 months post-NHC versus PD-extract injection. i, CTCF of s129p αS normalized to total αS, n = 5 mice per group. Two experiments, unpaired t-test. j, TH⁺ immunostainings in SNpc and VTA using DAB, 3 months post-treatment. brightfield micrograph of dopaminergic neurons in the SNpc. k, Unbiased stereological quantification of TH⁺ cells in SNpc and VTA, n = 7 mice for αS-NHC, SNpc and VTA, n = 8 mice for αS-PD, SNpc and VTA. Three experiments, mixed-effect model with multivariate t-distribution posthoc test. Data are mean ± s.e.m. (error bars). Scale bars, 100 μm (a,b), insets 20 μm (a,b,j); 20 μm (f,j); 50 μm (h); 500 µm (j). DA, dopaminergic.

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