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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author 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
author_facet 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
author_sort Li-Pao Fang
collection DOAJ
description 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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publishDate 2025-01-01
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series Nature Communications
spelling doaj-art-49dc4f9b9c734fc3a42706333fd8502c2025-02-02T12:33:23ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-025-56484-8Oligodendrocyte precursor cells facilitate neuronal lysosome releaseLi-Pao Fang0Ching-Hsin Lin1Yasser Medlej2Renping Zhao3Hsin-Fang Chang4Qilin Guo5Zhonghao Wu6Yixun Su7Na Zhao8Davide Gobbo9Amanda Wyatt10Vanessa Wahl11Frederic Fiore12Szu-Min Tu13Ulrich Boehm14Wenhui Huang15Shan Bian16Amit Agarwal17Marcel A. Lauterbach18Chenju Yi19Jianqin Niu20Anja Scheller21Frank Kirchhoff22Xianshu Bai23Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandMolecular Imaging, CIPMM, University of SaarlandBiophysics, CIPMM, University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandResearch Centre, Seventh Affiliated Hospital of Sun Yat-sen UniversityResearch Centre, Seventh Affiliated Hospital of Sun Yat-sen UniversityMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandThe Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg UniversityCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandInstitute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityThe Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg UniversityMolecular Imaging, CIPMM, University of SaarlandDepartment of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical UniversityResearch Centre, Seventh Affiliated Hospital of Sun Yat-sen UniversityMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandAbstract 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.https://doi.org/10.1038/s41467-025-56484-8
spellingShingle 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
Oligodendrocyte precursor cells facilitate neuronal lysosome release
Nature Communications
title Oligodendrocyte precursor cells facilitate neuronal lysosome release
title_full Oligodendrocyte precursor cells facilitate neuronal lysosome release
title_fullStr Oligodendrocyte precursor cells facilitate neuronal lysosome release
title_full_unstemmed Oligodendrocyte precursor cells facilitate neuronal lysosome release
title_short Oligodendrocyte precursor cells facilitate neuronal lysosome release
title_sort oligodendrocyte precursor cells facilitate neuronal lysosome release
url https://doi.org/10.1038/s41467-025-56484-8
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