Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia
作者机构：Department of EndocrinologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China The Chongqing Key Laboratory of Translational Medicine in Major Metabolic DiseasesThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Department of Nutrition and Food HygieneSchool of Public Health and ManagementChongqing Medical UniversityChongqing 400016PR China Department of NeurologyAffiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou 550004PR China Department of Nutrition and Food ScienceTexas A&M UniversityCollege StationTX 77843USA
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2022年第9卷第2期
页 面：401-414页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 0703[理学-化学] 10[医学]
基 金：This work was supported by the National Natural Science Foundation of China(No.81871222,81570763 and 81270947,to XX) the Fundamental Science and Advanced Technology Research of Chongqing(Major Project,No.CSTC2015jcyjB0146) the National Program on Key Basic Research Project(973 Program)of China(973 Program,No.2012CB517505,to XX)
主 题：Diabetes Microglial polarization Neurodegeneration Neuroinflammation Obesity TREM2
摘 要：Type 2 diabetes mellitus(T2DM)and Alzheimer s disease(AD)share several common pathophysiological *** variants of triggering receptor expressed on myeloid cells 2(TREM2)increase the risk of developing AD,suggesting the involvement of TREM2 and innate immunity in AD *** is still unknown whether TREM2 is related to cognitive impairment in ***,we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet(HFD)-fed *** C57BL/6J mice were maintained on HFD for 50 ***2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector(AAV)-mediated gene *** results showed that the HFD feeding induced rapid and persistent weight gain,glucose intolerance and significant impairments in learning and *** with AAV-con,AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD *** overexpression of TREM2 upregulated the synaptic proteins spinophilin,PSD95 and synaptophysin,suggesting the improvement in synaptic *** complexity and spine density in the CA1 region were rescued after TREM2 ***,TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus,suppressed neuroinflammation and microglial *** sum,hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory *** study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.
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