Fig. 5: Flea bites affect neural function through the skin-brain axis.

a GSEA result on upregulated genes from the mice skin transcriptome. Functions related to immunoglobulin and hemoglobin genes are significantly enriched. b Cytokine levels in mice skin presented in boxplot where red is Flea− (n = 6/12) and blue is Flea+ (n = 6/12). Two-sided t test was used. Asterisks indicate the significance. All p-values were below 0.001. c Cytokine levels in mice serum presented in boxplot where red is Flea− (n = 12) and blue is Flea+ (n = 12). Two-sided t test was used. Thick bars indicate the interquartile range (IQR) around the median, and whiskers represent 1.5 times the interquartile range (maxima: Q3 + 1.5 × IQR, minima: Q1 − 1.5 × IQR). Asterisks indicate the significance. All p-values were below 0.001. d Cytokine levels in mice PFC presented in boxplot where red is Flea− (n = 10) and blue is Flea+ (n = 10). Two-sided t test was used. Asterisks indicate the significance. All p-values were below 0.001. e Representative HE plots of the PFC. In the Flea+ group, cortical tissue shows evident cellular damage, with minor mononuclear cell infiltration (yellow arrow) at the injury site. Additionally, widespread nuclear pyknosis and condensation (red arrow) are observed in the parenchyma. The infected group exhibits a larger area of damage; Scale 50 µm. f Western blot analysis of Claudin1 markers of tight junction protein from the PFC brain region (n = 5 samples each group). g Comparison of Claudin1 in WB between the Flea− (red, n = 5) and Flea+ (blue, n = 5) groups of mice. Two-sided t test was used. Each black dot represents an individual. Asterisks indicates brain regions with significant differences. Data are presented as mean ± SEM. Source data are provided as a Source Data file. h Validation by qPCR of select BBB genes altered between Flea− (n = 3) and Flea+ (n = 3) group. Two-sided t test was used. Thick bars indicate the interquartile range (IQR) around the median, and whiskers represent 1.5 times the interquartile range (maxima: Q3 + 1.5 × IQR, minima: Q1 − 1.5 × IQR). Each black dot represents pooled sample of 3 decapitated individuals. Asterisks indicate the significance. ***p < 0.001, **p < 0.01, *p < 0.05.