Oligodendrocyte precursor cells facilitate neuronal lysosome release

Abstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neur...

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Main Authors: Li-Pao Fang, Ching-Hsin Lin, Yasser Medlej, Renping Zhao, Hsin-Fang Chang, Qilin Guo, Zhonghao Wu, Yixun Su, Na Zhao, Davide Gobbo, Amanda Wyatt, Vanessa Wahl, Frederic Fiore, Szu-Min Tu, Ulrich Boehm, Wenhui Huang, Shan Bian, Amit Agarwal, Marcel A. Lauterbach, Chenju Yi, Jianqin Niu, Anja Scheller, Frank Kirchhoff, Xianshu Bai
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56484-8
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Summary:Abstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer’s disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases.
ISSN:2041-1723