Fig. 7. BDNF as the only major neurotrophic factor down-regulated in foot skin of mice lacking skin keratinocyte-derived SIRT1.
(A) Dot plot based on scRNA-seq data (Supplementary Fig. 6) indicating the differential expression of neurotrophic factors in keratinocytes of foot skin between Control 1 (SIRT1flox/flox) and keratinocyte-specific SIRT1 KO mice. The size of the circles represents the percentage of cells expressing a given neurotrophic factor, and the color of the circles represents the expression level of that neurotrophic factor. Similar to SIRT1 KO, keratinocyte-specific BDNF KO developed more severe (B) static and (C) dynamic allodynia than the controls after 3 months of HFD. Statistics were performed by two-way ANOVA. (D) IF images of Meissner corpuscles and IHC images of free nerve endings in foot skin from BDNF KO and control mice. (E) IF images of Meissner corpuscles double stained with S100 and NFH. (F) Meissner corpuscle, (G) free nerve ending (IENFD) and (H) epidermal Aβ fiber densities in foot skin from BDNF KO and control mice. (I) Occasional Meissner corpuscle with abnormal morphology (filled arrowhead). Scale bars represent 100 μm for IF and 50 μm for IHC images. Error bars indicate SEM. Statistics were performed by Student’s t-test: ** p < 0.01, * p < 0.05, ns = non-significant.