Disodium Cromoglycate Attenuates the Depressive‐Like Behaviors in Mice by Inhibiting Neuroinflammation

ABSTRACT Aims Emerging evidence indicates that mast cells (MCs) may play a crucial role in the pathogenesis of major depression disorder (MDD). This study aimed to investigate whether the mast cell membrane stabilizer Disodium cromoglycate (DSCG) could ameliorate depressive‐like behaviors by attenuating mast cell‐mediated neuroinflammation. Methods Lipopolysaccharide (LPS)‐induced and chronic restraint stress (CRS)‐induced mouse models were induced in C57BL/6 mice to evaluate the therapeutic effect of the DSCG. Depressive‐like behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). Histopathological and molecular changes were examined through immunofluorescence, western blot, RT‐qPCR, and ELISA. Results Firstly, our results indicated that the number of MCs was increased in the brain from LPS‐induced depression model mice. Secondly, both CRS and LPS‐induced depressive‐like behaviors were significantly ameliorated by DSCG. Moreover, treatment with DSCG could down‐regulate the expression of MCs‐associated genes in the brain of depression model mice. Mechanically, our results displayed that the use of DSCG significantly suppressed the activation of glial cells and the expression of pro‐inflammatory factors. Conclusion Our study demonstrates that MCs infiltration and activation contribute to neuroinflammation in LPS‐induced depressive mice. DSCG exerts its antidepressant effects primarily by modulating MCs‐mediated neuroinflammation. These results highlight DSCG as a promising therapeutic candidate for the treatment of inflammation‐associated depression.