Up-Regulation of Trem2 Inhibits Hippocampal Neuronal Apoptosis and Alleviates Oxidative Stress in Epilepsy via the PI3K/Akt Pathway in Mice  

作　　者：Ai-Hua Liu Min Chu Yu-Ping Wang 

机构地区：[1]Department of Neurology, Xuanwu Hospital, Capital Medical University

出　　处：《Neuroscience Bulletin》2019年第3期471-485,共15页神经科学通报（英文版）

基　　金：supported by Beijing Key Laboratory of Neuromodulation(BZ0098);the Precision Medicine Project of the Ministry of Science and Technology of China(2016YFC0904400)

摘　　要：Epilepsy is a chronic and severe neurological disorder that has negative effects on the autonomous activities of patients. Functionally, Trem2(triggering receptor expressed on myeloid cells-2) is an immunoglobulin receptor that affects neurological and psychiatric genetic diseases. Based on this rationale, we aimed to assess the potential role of Trem2 integration with the PI3 K/Akt pathway in epilepsy. We used microarray-based gene expression profiling to identify epilepsy-related differentially-expressed genes. In a mouse hippocampal neuron model of epilepsy, neurons were treated with lowMg^2+ extracellular fluid, and the protein and mRNA expression of Trem2 were determined. Using a gain-offunction approach with Trem2, neuronal apoptosis and its related factors were assessed by flow cytometry, RT-qPCR,and Western blot analysis. In a pilocarpine-induced epileptic mouse model, the malondialdehyde(MDA) and8-hydroxy-20-deoxyguanosine(8-OHdG) content and superoxide dismutase(SOD) and glutathione-peroxidase(GSH-Px) activity in the hippocampus were determined,and the protein expression of Trem2 was measured. In addition, the regulatory effect of Trem2 on the PI3 K/Akt pathway was analyzed by inhibiting this pathway in both the cell and mouse models of epilepsy. Trem2 was found to occupy a core position and was correlated with epilepsy.Trem2 was decreased in the hippocampus of epileptic miceand epileptic hippocampal neurons. Of crucial importance,overexpression of Trem2 activated the PI3 K/Akt pathway to inhibit neuronal apoptosis. Moreover, activation of the PI3 K/Akt pathway through over-expression of Trem2 alleviated oxidative stress, as shown by the increased expression of SOD and GSH-Px and the decreased expression of MDA and 8-OHdG. The current study defines the potential role of Trem2 in inhibiting the development of epilepsy, indicating that Trem2 up-regulation alleviates hippocampal neuronal injury and oxidative stress, and inhibits neuronal apoptosis in epilepsy by activating the PI3 K/Akt pathway.Epilepsy is a chronic and severe neurological disorder that has negative effects on the autonomous activities of patients. Functionally, Trem2（triggering receptor expressed on myeloid cells-2） is an immunoglobulin receptor that affects neurological and psychiatric genetic diseases. Based on this rationale, we aimed to assess the potential role of Trem2 integration with the PI3 K/Akt pathway in epilepsy. We used microarray-based gene expression profiling to identify epilepsy-related differentially-expressed genes. In a mouse hippocampal neuron model of epilepsy, neurons were treated with lowMg2+ extracellular fluid, and the protein and mRNA expression of Trem2 were determined. Using a gain-offunction approach with Trem2, neuronal apoptosis and its related factors were assessed by flow cytometry, RT-qPCR,and Western blot analysis. In a pilocarpine-induced epileptic mouse model, the malondialdehyde（MDA） and8-hydroxy-20-deoxyguanosine（8-OHdG） content and superoxide dismutase（SOD） and glutathione-peroxidase（GSH-Px） activity in the hippocampus were determined,and the protein expression of Trem2 was measured. In addition, the regulatory effect of Trem2 on the PI3 K/Akt pathway was analyzed by inhibiting this pathway in both the cell and mouse models of epilepsy. Trem2 was found to occupy a core position and was correlated with epilepsy.Trem2 was decreased in the hippocampus of epileptic miceand epileptic hippocampal neurons. Of crucial importance,overexpression of Trem2 activated the PI3 K/Akt pathway to inhibit neuronal apoptosis. Moreover, activation of the PI3 K/Akt pathway through over-expression of Trem2 alleviated oxidative stress, as shown by the increased expression of SOD and GSH-Px and the decreased expression of MDA and 8-OHdG. The current study defines the potential role of Trem2 in inhibiting the development of epilepsy, indicating that Trem2 up-regulation alleviates hippocampal neuronal injury and oxidative stress, and inhibits neuronal apoptosis in epilepsy by activating the PI3 K/Akt

关 键 词：Trem2 EPILEPSY NEURONAL apoptosis PI3K/Akt pathway OXIDATIVE stress 

分 类 号：R[医药卫生]