Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia
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....
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-03-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300702 |
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| author | Min Wu Maolin Liao Rongfeng Huang Chunxiu Chen Tian Tian Hongying Wang Jiayu Li Jibin Li Yuxiang Sun Chaodong Wu Qifu Li Xiaoqiu Xiao |
| author_facet | Min Wu Maolin Liao Rongfeng Huang Chunxiu Chen Tian Tian Hongying Wang Jiayu Li Jibin Li Yuxiang Sun Chaodong Wu Qifu Li Xiaoqiu Xiao |
| author_sort | Min Wu |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-1cba5398494d4b87a7943b658915a6ab |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T08:33:32Z |
| publishDate | 2022-03-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj.art-1cba5398494d4b87a7943b658915a6ab2023-09-02T17:25:16ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422022-03-0192401414Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microgliaMin Wu0Maolin Liao1Rongfeng Huang2Chunxiu Chen3Tian Tian4Hongying Wang5Jiayu Li6Jibin Li7Yuxiang Sun8Chaodong Wu9Qifu Li10Xiaoqiu Xiao11Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaThe Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USADepartment of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USADepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; Corresponding author. Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.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.http://www.sciencedirect.com/science/article/pii/S2352304220300702DiabetesMicroglial polarizationNeurodegenerationNeuroinflammationObesityTREM2 |
| spellingShingle | Min Wu Maolin Liao Rongfeng Huang Chunxiu Chen Tian Tian Hongying Wang Jiayu Li Jibin Li Yuxiang Sun Chaodong Wu Qifu Li Xiaoqiu Xiao Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia Genes and Diseases Diabetes Microglial polarization Neurodegeneration Neuroinflammation Obesity TREM2 |
| title | Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia |
| title_full | Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia |
| title_fullStr | Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia |
| title_full_unstemmed | Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia |
| title_short | Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia |
| title_sort | hippocampal overexpression of trem2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia |
| topic | Diabetes Microglial polarization Neurodegeneration Neuroinflammation Obesity TREM2 |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300702 |
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