Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (8): 1770-1776.doi: 10.4103/1673-5374.363187

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Microglia and astrocytes mediate synapse engulfment in a MER tyrosine kinase-dependent manner after traumatic brain injury

Hui Shen1, Xiao-Jing Shi1, Lin Qi1, Cheng Wang1, Muyassar Mamtilahun1, Zhi-Jun Zhang1, Won-Suk Chung2, *, Guo-Yuan Yang1, *, Yao-Hui Tang1, *#br#   

  1. 1Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; 2Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea
  • Online:2023-08-15 Published:2023-02-23
  • Contact: Guo-Yuan Yang, MD, PhD, gyyang@sjtu.edu.cn; Yao-Hui Tang, PhD, yaohuitang@sjtu.edu.cn; Won-Suk Chung, PhD, wonsuk.chung@kaist.ac.kr.
  • Supported by:
    This study was supported by the National Key R&D Program of China, No. 2019YFA0112000 (to YHT); the National Natural Science Foundation of China, Nos. 82071284 (to YHT), 81974179 (to ZJZ); Shanghai Rising-Star Program, No. 21QA1405200 (to YHT); the Scientific Research and Innovation Program of Shanghai Education Commission, No. 2019-01-07-00-02-E00064 (to GYY); Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission, No. 20JC1411900 (to GYY); the National Research Foundation of Korea, Nos. 2020M3E5D9079912 (to WSC), 2021R1A2C3005704 (to WSC), 2022M3E5E8081188 (to WSC); and the Korea Health Technology R&D Project, No. HU20C0290 (to WSC).

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Abstract: Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models, but it is unclear whether the same mechanism is also active in traumatic brain injury. In this study, we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury. Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function. In addition, in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice, the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased, and the total number of dendritic spines was increased. Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis, and inhibiting this process could be a new strategy for treating traumatic brain injury.

Key words: animal model, astrocyte, dendritic spines, lysosome, macrophage, MER proto-oncokinase, microglia, neurologic function, phagocytosis, synapse engulfment, traumatic brain injury