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

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.