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Fig. 6 | Journal of Neuroinflammation

Fig. 6

From: Bruton’s tyrosine kinase drives neuroinflammation and anxiogenic behavior in mouse models of stress

Fig. 6

Pharmacological inhibition of BTK with ibrutinib attenuates hyper-anxious behavior as well as proinflammatory molecules in the hippocampus of stressed mice. Mice subjected to restraint stress and underwater trauma was injected with ibrutinib (3 mg/kg, i.p.) or vehicle. A Immunoblot analysis of pBTK in hippocampal homogenates. B The relative densitometry of pBTK immunoblots from hippocampal samples showing ibrutinib treatment significantly reduced the pBTK levels in physically stressed mice as compared to vehicle-treated stressed mice. All values are presented as mean with 95% CI (n = 6/group); ***p < 0.001, **p < 0.01 ns (not significant); 2X2 factorial ANOVA followed by Bonferroni post hoc test. C Immunoblot analysis of NLRP3 in hippocampus homogenates D The relative densitometry of NLRP3 immunoblots from hippocampal samples showing ibrutinib treatment significantly reduced the NLRP3 inflammasome levels in physically stressed mice as compared to vehicle-treated stressed mice. ***p < 0.001, ns (not significant); One way ANOVA, followed by Bonferroni post hoc test E Open field test: physically stressed mice dosed with ibrutinib exhibited significantly decreased anxiety levels when compared to the vehicle controls, as illustrated by increased exploration time in the central area of the OFT. F Light–dark test: physically stressed mice dosed with ibrutinib exhibited significant rescue from hyper-anxiety as explained by the significant increase in their time spent in the light chamber of the LDT (G). Elevated plus maze test: physically stress mice injected with ibrutinib displayed significantly reduced anxiety, as evidenced by the increased duration of time spent in the open arms of the EPM. H Analysis of IL1β in the hippocampus by ELISA revealed physically stressed mice dosed with ibrutinib showed diminished proinflammatory IL1β. I Caspase 1 activity in the hippocampus: administration of ibrutinib in physically stressed mice showed reduced Caspase 1 activation, elucidating significant rescue from the anxiogenic proinflammatory pathway. All values are presented as mean with 95% CI (n = 22/group); ***p < 0.001, ns (not significant); 2X2X2 factorial ANOVA, followed by Bonferroni post hoc test

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