Fig. 4

Microglia-specific TRPV1 deficiency accelerates PFF-induced PD-like pathology in TRPV1^flox/flox; Cx3cr1^Cre mice. a Representative TEM images of α-synuclein monomers, pre-sonicated PFFs and post-sonicated PFFs. Scale bar, 200 nm. b Schematic diagram showing PFF experimental design. IF, immunofluorescence; IHC, immunohistochemistry. c–g Behavioral assessment of TRPV1^flox/flox and TRPV1^flox/flox; Cx3cr1^Cre mice following a single unilateral inoculation of PBS or PFF into the striatum. PFF-injected TRPV1^flox/flox (n = 11) and TRPV1^flox/flox; Cx3cr1^Cre mice (n = 9), as well as age-matched PBS-injected TRPV1^flox/flox (n = 10) and TRPV1^flox/flox; Cx3cr1^Cre animals (n = 7) are also shown. c–d Rotarod test, and e–g open field test. h–k Representative immunohistochemistry images h and quantification of p-α-syn (Ser129) aggregates in SNpc (i), hippocampus j and cortex k of mice killed 6 months after striatal PFF injection (n = 3 animals per group). Scale bar, 50 μm. One-way ANOVA was used for statistical analysis followed by Tukey’s multiple comparisons test in d–k. Two-way ANOVA was used for statistical analysis followed by Tukey’s multiple comparisons test in c. Error bars represent mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001