Up-Regulation of Trem2 Inhibits Hippocampal Neuronal Apoptosis and Alleviates Oxidative Stress in Epilepsy via the PI3K/Akt Pathway in Mice.
10.1007/s12264-018-0324-5
- Author:
Ai-Hua LIU
1
;
Min CHU
1
;
Yu-Ping WANG
2
Author Information
1. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
2. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. yupingwang01@sina.cn.
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Neuronal apoptosis;
Oxidative stress;
PI3K/Akt pathway;
Trem2
- MeSH:
Animals;
Apoptosis;
Cells, Cultured;
Epilepsy;
metabolism;
Gene Expression Profiling;
Hippocampus;
metabolism;
Male;
Membrane Glycoproteins;
metabolism;
Mice, Inbred ICR;
Neurons;
metabolism;
Oxidative Stress;
Phosphatidylinositol 3-Kinase;
metabolism;
Proto-Oncogene Proteins c-akt;
metabolism;
Receptors, Immunologic;
metabolism;
Signal Transduction;
Up-Regulation
- From:
Neuroscience Bulletin
2019;35(3):471-485
- CountryChina
- Language:English
-
Abstract:
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 PI3K/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 low-Mg extracellular fluid, and the protein and mRNA expression of Trem2 were determined. Using a gain-of-function 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) and 8-hydroxy-2'-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 PI3K/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 mice and epileptic hippocampal neurons. Of crucial importance, overexpression of Trem2 activated the PI3K/Akt pathway to inhibit neuronal apoptosis. Moreover, activation of the PI3K/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 PI3K/Akt pathway.
