Fig. 8: TRPV1 genetic deficiency exacerbated recognition impairment and neuronal lipid droplet accumulation in ApoE4 mice.

a–c MWM for TRPV1^−/−-ApoE3 and TRPV1^−/−-ApoE4 mice. Line chart shows MWM escape latency (time to find the hidden platform) for six consecutive days (a). Histograms show time spent in the target quadrant and times crossing the platform location in the MWM probe trial (b, c). d Immunofluorescent images in the left panel show cortical sections of ApoE3 and ApoE4 mice stained for BODIPY and NeuN. The right panel shows 3D reconstructions of BODIPY⁺NeuN⁺ neuronal soma. e Volume of BODIPY⁺ puncta in NeuN⁺ cells in the cerebral cortex. f Volcano plot showing differentially expressed genes between ApoE4 and TRPV1^−/−-ApoE4 mouse brains. Dotted lines indicate the p < 0.05 cutoff (n = 3 mice per group; two-sided Student’s t test, Benjamini‒Hochberg FDR). g Enrichment pathway analysis of genes differentially expressed in ApoE4 and TRPV1^−/−-ApoE4 mouse brains. h Heatmap showing gene expression profiles enriched in the MHC-I pathway in TRPV1^−/−-ApoE3 and TRPV1^−/−-ApoE4 mice. i, j Representative immunofluorescent images and quantification of NeuN⁺ and B2M⁺ cells in the cortex of ApoE3 and ApoE4 mice. k Representative immunofluorescence micrographs of ApoE3 and ApoE4 mouse cerebral cortex stained for Iba-1 and PSD95 (left panel) and 3D reconstruction (right panel) showing the volume of Iba-1 (green) and engulfed PSD95 puncta (red). l Quantification of PSD95 puncta numbers and Iba-1 engulfed from immunofluorescent images. n = 3 mice per group. Statistical tests: one-way ANOVA followed by Tukey’s post hoc test (b, c, e, g, j, l) and two-way ANOVA followed by Tukey’s post hoc test (a). Data represent the mean ± s.e.m. *p < 0.05, **p < 0.01, ****p < 0.0001. Scale bars, 25 μm.