Microglial glutaminase 1 deficiency mitigates neuroinflammation associated depression

• DOI: 10.1016/j.bbi.2021.10.009
• Publication Date: 2021-10-20T04:36:05Z
• Authors: Chenhui Ji; Yalin Tang; Yanyan Zhang; Congcong Li; Huazheng Liang; Lu Ding; Xiaohuan Xia; Lize Xiong; Xin-Rui Qi; Jialin C. Zheng
• Keywords: Glutaminase

Glutaminase 1 (GLS1) has recently been reported to be expressed in microglia and plays a crucial role neuroinflamation. Significantly increased level of GLS1 mRNA expression together with neuroinflammation pathway were observed postmortem prefrontal cortex from depressed patients. To find out the function microglial depression neuroinflammation, we generated transgenic mice (GLS1 cKO), postnatally losing microglia, detect changes lipopolysaccharide (LPS)-induced model. LPS-induced anxiety/depression-like behavior was attenuated cKO mice, paralleled by significant reduction pro-inflammatory cytokines an abnormal morphological phenotype cortex. Reduced deficient result less reactive astrocytes, as deficiency enhanced miR-666-3p miR-7115-3p levels extracellular vesicles released thus suppressing astrocyte activation via inhibiting Serpina3n expression. Together, our data reveal novel mechanism targeting may strategy alleviate neuroinflammation-related other disease.