Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia

Min Wu; Maolin Liao; Rongfeng Huang; Chunxiu Chen; Tian Tian; Hongying Wang; Jiayu Li; Jibin Li; Yuxiang Sun; Chaodong Wu; Qifu Li; Xiaoqiu Xiao

doi:10.1016/j.gendis.2020.05.005

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Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia

更新时间：2022-06-24

- Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia
- Genes & Diseases Vol. 9, Issue 2, (2022)
- 作者机构：
  
  1. Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University,Chongqing,PR China,400016
  2. The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University,Chongqing,PR China,400016
  3. Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University,Chongqing,PR China,400016
  4. Department of Neurology, Affiliated Hospital of Guizhou Medical University,Guizhou,Guiyang,PR China,550004
  5. Department of Nutrition and Food Science, Texas A&M University, College Station,TX,USA,77843
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.05.005
  CLC：
- Published：2022，
  
  Published Online：1 March 2022，
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Min Wu, Maolin Liao, Rongfeng Huang, et al. Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia. [J]. Genes & Diseases 9(2).(2022)
DOI：

Min Wu, Maolin Liao, Rongfeng Huang, et al. Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia. [J]. Genes & Diseases 9(2).(2022) DOI： 10.1016/j.gendis.2020.05.005.

摘要

Abstract

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share several common pathophysiological features. Rare 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 development. It is still unknown whether TREM2 is related to cognitive impairment in T2DM. Here

we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet (HFD)-fed mice. Male C57BL/6J mice were maintained on HFD for 50 weeks. TREM2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector (AAV)-mediated gene delivery. The results showed that the HFD feeding induced rapid and persistent weight gain

glucose intolerance and significant impairments in learning and memory. Compared with AAV-con

AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD mice. The overexpression of TREM2 upregulated the synaptic proteins spinophilin

PSD95 and synaptophysin

suggesting the improvement in synaptic transmission. Dendritic complexity and spine density in the CA1 region were rescued after TREM2 overexpression. Furthermore

TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus

suppressed neuroinflammation and microglial activation. In sum

hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory phenotype. Our study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.

关键词

Keywords

DiabetesMicroglial polarizationNeurodegenerationNeuroinflammationObesityTREM2

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