Fig. 2: TRPV1 knock-out in 5×FAD mice has nonsignificant effect on the capsaicin-mediated amelioration in AD pathologies.
a Distribution of capsaicin in digestive tracts and different tissues of 5×FAD mice following repeated administration. n = 3 mice in each group. Data are presented as mean ± SD. b A cartoon showing the breeding scheme of 5×FAD & TRPV1–/– (KO) mice. Created in BioRender. Zheng, J. (2026) https://BioRender.com/c9dsmfb. c, d Representative immunofluorescent images and blots showing the expression and knock-out of TRPV1 in different tissues. (e–h) TRPV1 KO in both veh- and cap-treated 5×FAD mice did not significantly change Aβ plaques (f), microglia soma volume (g) and cell processes complexity (h). White circles in representative images indicate plaque-surrounded cell aggregates, arrows point to cells showed in 3D-reconstruced images (e). Crosses indicate individual cells and circles indicate mean values of individual mouse (h). Bands indicate SD (g). n = 5 mice or 15 cells in each group. Data are presented as mean ± SD. Two-way ANOVA followed by Tukey’s multiple comparisons test. Statistics of panel (g): 5×FAD+Veh vs 5×FAD&KO+Veh, P = 0.79 (n.s.); 5×FAD+Cap vs 5×FAD&KO+Cap, P = 0.98 (n.s.); 5×FAD +Veh vs 5×FAD+Cap, **P = 0.0002; 5×FAD&KO+Veh vs 5×FAD&KO+Cap, **P = 0.01. i TRPV1 KO induced nonsignificant change in inflammatory factors, and did not alter the effect of capsaicin on downregulating IL-1β and TNF-α. Data were normalized by the mean value of Veh+5×FAD group for each inflammatory factor. n = 5 mice in each group. Data are presented as mean ± SD. Two-way ANOVA followed by Tukey’s multiple comparisons test. j,k TRPV1 KO neither change the baseline object-place recognition of 5xFAD mice, nor abolish the cognitive-improving effect of capsaicin. Representative heatmaps (j) showed the time distribution of mice spent in test chambers. n = 10 mice in each group. Data are presented as mean ± SD. Two-way ANOVA followed by Tukey’s multiple comparisons test. TRPV1 KO had limited effects on baseline spatial learning (l) and memory (n) of 5xFAD mice, and did not cancel the cognitive-enhancing effects of capsaicin in Morris-water maze test. Representative images showed the trajectories of mice swimming in the water maze during the test phase, and cyan areas indicate the target quadrant in water maze (m). n = 10 mice in each group. Data are presented as mean ± SD. n.s. nonsignificant, repeated measures (l) or two-way (n) ANOVA followed by Tukey’s multiple comparisons test. Statistics of panel (l): 5×FAD+Veh vs 5×FAD&KO+Veh, P = 0.10 (n.s.); 5×FAD+Cap vs 5×FAD&KO+Cap, P = 0.70 (n.s.); 5×FAD +Veh vs 5×FAD+Cap, P = 0.0002**; 5×FAD&KO+Veh vs 5×FAD&KO+Cap, P = 0.0001**. Source data are provided as a Source Data file.
