Fig. 4.

Human-α-syn overexpression in DA neurons induces axonal pathology in connected brain regions. (a) Representative confocal images showing h-α-syn protein co-localised with TH⁺ fibres in DA output brain regions such as CPu, and motor, cingulate and visual cortices of AAV5-injected mice examined at 1, 4, 8 and 16 weeks (W) later. TH⁺ and h-α-syn⁺ fibres are identified with white arrowheads. Scale bar: 25 μm. Likewise, a representative image shows h-α-syn⁺ axonal swellings in motor cortex assessed by immunohistochemistry procedure. Axonal swellings are identified with black arrowheads. Scale bar: 100 μm. (b) Progressive accumulation of h-α-syn⁺ axonal swelling density in the different brain areas examined. (c) Progressive increases of h-α-syn⁺ fibre density in the different brain area examined. (d) Density of TH⁺ fibres in different DA innervated brain regions of mice. Overexpression of h-α-syn in SNc/VTA did not induce loss of DA terminals at 1, 4, 8 and 16 W post-infection (n = 3–5 mice/group; *P < 0.05, **P < 0.01, ***P < 0.001 versus to AAV5-injected mice and sacrificed 1 W later; two-way ANOVA and Tukey's multiple comparisons test). See also Supplementary Figs. 3 and 4.