In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke  

作　　者：Meng Yuan Yao Tang Tianwen Huang Lining Ke En Huang 

机构地区：[1]Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province,Fujian Medical University,Fuzhou,Fujian Province,China [2]Department of Human Anatomy,School of Basic Medical Sciences,Fujian Medical University,Fuzhou,Fujian Province,China [3]Scientific Research Center,School of Basic Medical Sciences,Fujian Medical University,Fuzhou,Fujian Province,China [4]Department of Neurology,Fujian Medical University Union Hospital,Fuzhou,Fujian Province,China [5]Fujian Key Laboratory of Vascular Aging,Fujian Medical University,Fuzhou,Fujian Province,China

出　　处：《Neural Regeneration Research》2024年第10期2240-2248,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82071418;the Natural Science Foundation of Fujian Province,No.2020J01612 (both to EH)。

摘　　要：In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

关 键 词：astrocyte in situ direct reprogramming ischemic stroke miR-30 based shRNA neuron polypyrimidine tract-binding protein 1 TRANSDIFFERENTIATION 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]