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

## TL;DR

This study shows that Disodium Cromoglycate reduces depressive-like behaviors in mice by reducing brain inflammation caused by mast cells.

## Contribution

The study identifies Disodium Cromoglycate as a potential treatment for depression by targeting mast cell-mediated neuroinflammation.

## Key findings

- Mast cells were increased in the brains of depression model mice.
- Disodium Cromoglycate reduced depressive-like behaviors in both LPS and CRS models.
- The drug downregulated mast cell-associated genes and pro-inflammatory factors in the brain.

## Abstract

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.

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.

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.

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.

Mast cells were increased in the brain of depression model mice. Administration of Disodium Cromoglycate could alleviate depressive‐like behaviors in mice of LPS and CRS models. Administration of Disodium Cromoglycate mitigated the infiltration of mast cells in brain and down‐reuglated the expression of pro‐inflammatory factors in the brain of depression model mice.