Fig. 4: TRPV1 activation rescued memory impairment and neuronal loss in ApoE4 HFD-fed mice.

a, b Novel object recognition and Y maze behavioral assessments for ApoE3 and ApoE4 HFD-fed mice with capsaicin treatment. c–e MWM behavioral assessment of ApoE3 and ApoE4 mice. c Line chart shows MWM escape latency (time to find the hidden platform) for six consecutive days. Histograms show the time spent in the target quadrant (d) and the number of platform location crossings (e) in the MWM probe trial. n = 5, 7, 5, 5, 4, 4 mice per group during behavioral assessments (a–e). f, g Representative immunofluorescent images and quantification of NeuN+ cells in the cerebral cortex and hippocampus of ApoE3 and ApoE4 HFD-fed mice treated with capsaicin. h, i Phosphorylated tau (AT-8)-covered area in the hippocampus of ApoE3, ApoE3 HFD-fed, ApoE4, and ApoE4 HFD-fed mice treated with capsaicin. n = 3 mice per group (f, h). Statistical tests: one-way ANOVA followed by Tukey’s post hoc test (a, b, d, e, g, i) and two-way ANOVA followed by Tukey’s post hoc test (c). Data represent the mean ± s.e.m. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Scale bars, 30 μm (f); 300 μm (h).