MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination

作     者：Xiaohong Dong Zhi Zhang Xin Shu Zi Zhuang Pinyi Liu Renyuan Liu Shengnan Xia Xinyu Bao Yun Xu Yan Chen 

作者机构：Department of NeurologyNanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of NeurologyNanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210008China Department of NeurologyDrum Tower Hospital of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular MedicineMedical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of NeurologyNanjing210008China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2024年第40卷第4期

页      面：483-499页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81801147 and 81971112) 

主　　题：White matter injury Cognitive dysfunction MFG-E8 Remyelination Microglial phagocytosis 

摘      要：Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter *** phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white ***,milk fat globule-epidermal growth factor-factor 8(MFG-E8),a microglial phagocytosis-related protein,has not been well studied in hypoperfusion-related cognitive *** found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis(BCAS).MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral *** addition,we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron ***,MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after ***,in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via theαVβ3/αVβ5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature ***,we found that MFG-E8 was mainly derived from astrocytes,not *** findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.