Oligodendrocyte precursor cells facilitate neuronal lysosome release.

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

Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, 66421, Homburg, Germany.Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, 66421, Homburg, Germany. · pubmed

Paper

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.

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Research summary

Oligodendrocyte precursor cells facilitate the exocytosis of neuronal lysosomes, which is linked to altered metabolism and senescence in neurons with age. The study addresses mechanisms that may contribute to age-related pathologies, suggesting potential avenues for intervention in neurodegenerative diseases.

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