AUTHOR=Li Xiaoheng , Peng Zhixin , Jiang Lingling , Zhang Ping , Yang Pin , Yuan Zengqiang , Cheng Jinbo 

TITLE=Dlg1 deletion in microglia ameliorates chronic restraint stress induced mice depression-like behavior

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1124845

DOI=10.3389/fphar.2023.1124845

ISSN=1663-9812

ABSTRACT=Major depression is one of the most common psychiatric disorders worldwide, inflicting suffering, significant reduction in life span, and financial burdens on families and society. Mounting evidence implicates that exposure to chronic stress can induce the dysregulation of the immune system, and the activation of brain-resident innate immune cells, microglia, leading to depression-like symptoms. However, the specific mechanisms need to be further elucidated. In our previous work, we found that Discs large homolog 1 (Dlg1) deletion in microglia alleviates LPS-induced depression. Here, we adopt chronic restraint stress (CRS)-induced depression model, a commonly used paradigm without exaggerated inflammation and mimics the etiology of depression. We found that Dlg1 knockout ameliorates CRS-induced mice depression-like behavior. In contrast to the effect of Dlg1 in the LPS-induced mouse model, Dlg1 knockout had little effect on microglial density, but significantly decreased the number of activated microglia and reversed microglia morphological changes in mice exposed to CRS. Collectively, we provide evidence that Dlg1 plays a critical role in depression by regulating microglial activation, implicating a potential target for the treatment of clinical depression.