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

Neural Regen Res

Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, Fuzhou, Fujian Province, China.

Published: October 2024

JOURNAL/nrgr/04.03/01300535-202410000-00025/figure1/v/2024-02-06T055622Z/r/image-tiff 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.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034579PMC
http://dx.doi.org/10.4103/1673-5374.390957DOI Listing

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