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Oligodendrocyte precursor cells facilitate neuronal lysosome release

Author

Listed:
  • Li-Pao Fang

    (University of Saarland
    China Pharmaceutical University
    University of Saarland)

  • Ching-Hsin Lin

    (University of Saarland
    University of Saarland)

  • Yasser Medlej

    (University of Saarland)

  • Renping Zhao

    (University of Saarland)

  • Hsin-Fang Chang

    (University of Saarland
    University of Saarland)

  • Qilin Guo

    (University of Saarland)

  • Zhonghao Wu

    (Seventh Affiliated Hospital of Sun Yat-sen University)

  • Yixun Su

    (Seventh Affiliated Hospital of Sun Yat-sen University
    Third Military Medical University)

  • Na Zhao

    (University of Saarland
    University of Saarland)

  • Davide Gobbo

    (University of Saarland)

  • Amanda Wyatt

    (University of Saarland
    Saarland University School of Medicine)

  • Vanessa Wahl

    (University of Saarland
    Saarland University School of Medicine)

  • Frederic Fiore

    (Heidelberg University
    Heidelberg University)

  • Szu-Min Tu

    (University of Saarland
    University of Saarland)

  • Ulrich Boehm

    (University of Saarland
    Saarland University School of Medicine)

  • Wenhui Huang

    (University of Saarland)

  • Shan Bian

    (Tongji University)

  • Amit Agarwal

    (Heidelberg University
    Heidelberg University)

  • Marcel A. Lauterbach

    (University of Saarland)

  • Chenju Yi

    (Third Military Medical University)

  • Jianqin Niu

    (Seventh Affiliated Hospital of Sun Yat-sen University)

  • Anja Scheller

    (University of Saarland
    University of Saarland)

  • Frank Kirchhoff

    (University of Saarland
    University of Saarland)

  • Xianshu Bai

    (University of Saarland
    China Pharmaceutical University
    University of Saarland)

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.

Suggested Citation

  • 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 , 2025. "Oligodendrocyte precursor cells facilitate neuronal lysosome release," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56484-8
    DOI: 10.1038/s41467-025-56484-8
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    References listed on IDEAS

    as
    1. Dwight E. Bergles & J. David B. Roberts & Peter Somogyi & Craig E. Jahr, 2000. "Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus," Nature, Nature, vol. 405(6783), pages 187-191, May.
    2. 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 , 2025. "Oligodendrocyte precursor cells facilitate neuronal lysosome release," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    3. Li-Pao Fang & Na Zhao & Laura C. Caudal & Hsin-Fang Chang & Renping Zhao & Ching-Hsin Lin & Nadine Hainz & Carola Meier & Bernhard Bettler & Wenhui Huang & Anja Scheller & Frank Kirchhoff & Xianshu Ba, 2022. "Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Xiao Zhang & Yao Liu & Xiaoqi Hong & Xia Li & Charles K. Meshul & Cynthia Moore & Yabing Yang & Yanfei Han & Wei-Guang Li & Xin Qi & Huifang Lou & Shumin Duan & Tian-Le Xu & Xiaoping Tong, 2021. "NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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