中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1770-1776.doi: 10.4103/1673-5374.363187

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

小胶质细胞或星形胶质细胞通过MER原癌激酶介导创伤性脑损伤后的突触吞噬

  

  • 出版日期:2023-08-15 发布日期:2023-02-23
  • 基金资助:
    国家重点研发计划项目(2019YFA0112000);国家自然科学基金项目(82071284,81974179);上海新星计划项目(21QA1405200);上海市教委科研创新计划项目(2019-01-07-00-02-E00064);上海市科委科技创新项目(20JC1411900);韩国国家研究基金项目(2020M3E5D9079912,2021R1A2C3005704,2022M3E5E8081188);韩国卫生技术研发项目(HU20C0290)

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).

摘要:

最近有研究显示,在发育或者脑卒中等模型中,小胶质细胞/巨噬细胞和星形胶质细胞可通过MER原癌激酶介导突触吞噬,但是否也以同样的机制在创伤性脑损伤后发挥作用,目前尚不清楚。为此,实验建立了创伤性脑损伤小鼠模型,14d后可见脑组织中MER原癌激酶表达增加。而特异性敲除小胶质细胞/巨噬细胞或星形胶质细胞中的MER原癌激酶,则创伤性脑损伤小鼠的脑损伤体积明显缩小,且其神经行为功能显著改善。此外在MER原癌激酶敲除小鼠中,吞噬突触的小胶质细胞/巨噬细胞和星形胶质细胞数量均显著减少,而树突棘总数增加。因此推测,小胶质细胞/巨噬细胞和星形胶质细胞中的MER原癌激酶在突触吞噬中起着重要的作用,且抑制其吞噬能力成为治疗创伤性脑损伤的新策略。

https://orcid.org/0000-0003-3105-9307 (Guo-Yuan Yang)

关键词: 星形胶质细胞, 小胶质细胞, 巨噬细胞, 突触吞噬, 创伤性脑损伤, MER原癌激酶, 吞噬, 树突棘, 动物模型, 神经功能, 溶酶体

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