Fig. 3: Conditional knockdown of Cldn5 expression in the PFC is sufficient to induce anxiety- and depressive-like behaviours. | Nature Communications

Fig. 3: Conditional knockdown of Cldn5 expression in the PFC is sufficient to induce anxiety- and depressive-like behaviours.

From: Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

Fig. 3

a Experimental timeline of prefrontal cortex (PFC) bilateral injection of AAV-shRNA of AAV-shRNA-Cldn5 viruses and behavioural studies. b Cldn5 mRNA (**p = 0.0021) and protein (*p = 0.0403) levels are reduced following AAV-shRNA-Cldn5 injection in the PFC of female mice compared to that in AAV-shRNA-injected mice, following doxycycline (Dox) treatment. Scale bars, 20μm. Subthreshold microdefeat (stressed mice) did not have a significant effect on anxiety- and depressive-like behaviours in the elevated plus maze (c), splash test (d), sucrose preference test at 48 h (**p = 0.0064 unstressed AAV-shRNA vs AAV-shRNA-Cldn5; **p = 0.0034 stressed AAV-shRNA vs AAV-shRNA-Cldn5) (e), forced swim test (f, FST) and for social interactions (*p = 0.0317 unstressed AAV-shRNA vs stressed AAV-shRNA; **p = 0.0089 unstressed AAV-shRNA-Cldn5 vs stressed AAV-shRNA-Cldn5) (g) tests. h However, main virus effects are observed when comparing all AAV-shRNA vs AAV-shRNA-Cldn5 animals (*p = 0.0129 for elevated plus maze; **p = 0.0084 for splash test; ****p < 0.0001 for sucrose preference at 24 h; *p = 0.0453 for forced swim test). i Intraindividual correlation of different behavioural data points reveals trends between anxiety- and depressive-like behaviours. P values in the boxes refer to the strength of the correlation between behaviours. j Experimental timeline of PFC bilateral injection of AAV-shRNA or AAV-shRNA-Cldn5 viruses and social interaction (SI) tests. k No significant difference in SI ratio was observed when a male social target (aggressor, AGG) was present, but a significant difference was found when a female AGG was present (*p = 0.0123). l SI ratios with male and female AGG values are significantly correlated to each other, and with Cldn5 mRNA levels. Data represent mean ± s.e.m; the number of animals or subjects (n) is indicated on graphs. Two-way ANOVA followed by Bonferroni’s multiple comparison test for behaviours, Correlations were evaluated with Pearson’s correlation coefficient; 2-group comparisons were evaluated with unpaired t-tests. *p < 0.05; **p < 0.01; ****p < 0.0001. Source data are provided as a Source Data file.

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