Microglial glutaminase 1 mediates chronic restraint stress-induced depression-like behaviors and synaptic damages  

作　　者：Huili Chen Shengyang Fu Xiangyu Li Meng Shi Jiazhen Qian Shu Zhao Ping Yuan Lu Ding Xiaohuan Xia Jialin C.Zheng 

机构地区：[1]Center for Translational Neurodegeneration and Regenerative Therapy,Tongji Hospital affiliated to Tongji University School of Medicine,200065 Shanghai,China [2]Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai,China [3]Translational Research Institute of Brain and Brain-Like Intelligence,Shanghai Fourth People’s Hospital affiliated to Tongji University School of Medicine,200434 Shanghai,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第1期40-43,共4页信号转导与靶向治疗（英文）

基　　金：supported in part by research grants from the National Natural Science Foundation of China(Nos.91949204 and 81830037 to J.C.Z.,Nos.81971145 and 82271477 to X.X.);Independent Original Basic Research Program of Tongji University(No.22120220596 to X.X.).

摘　　要：Dear Editor,Major depressive disorder(MDD)is one of the most common psychiatric illnesses that significantly increase the risk of suicide.1 Stress-triggered dysfunctions of microglia have been identified as a commonly occurred pathological feature of MDD.1–3 Microglial dysfunction contributes to the pathogenesis of MDD via immunoresponses/neuroinflammation-mediated neural damage and pathological synapse loss-mediated neural circuit disruption.1 Although the involvement of microglia in MDD has been widely investigated,the molecular mechanisms underlying microglial dysfunction remain largely unknown.Recently,we identified glutaminase 1(Gls1)as one key protein that participates in microglial dysfunction.4–6 Gls1 catalyzes the hydrolysis of glutamine to produce glutamate in the brain.4 Besides its well-known role in excitatory neurotoxicity,we found Gls1 up-regulation in microglia in animal models of Alzheimer’s disease and ischemic stroke.4,7 Gls1 activates microglia to overproduce cytokines and release inflammatory extracellular vesicles,therefore leading to neuroinflammation in animal models of Alzheimer’s disease and ischemic stroke.4–6 More importantly,Gls1 has been found to be up-regulated in the brains of MDD patients,and microglial Gls1 deficiency mitigated LPS-induced depression-like behaviors.8 However,LPS exposure is not an appropriate model to mimic MDD phenotypes,leaving the involvement of Gls1 in MDD an undetermined question.

关 键 词：INVOLVEMENT INFLAMMATION media 

分 类 号：R749.4[医药卫生—神经病学与精神病学]