Oligodendrocyte precursor cells facilitate neuronal lysosome release

L Li-Pao Fang C Ching-Hsin Lin Y Yasser Medlej R Renping Zhao H Hsin-Fang Chang (Department of Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University) Q Qilin Guo Z Zhonghao Wu Y Yixun Su N Na Zhao D Davide Gobbo A Amanda Wyatt V Vanessa Wahl (Max-Planck Institut für Molekulare Pflanzenphysiologie) F Frederic Fiore S Szu-Min Tu (Department of Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University) U Ulrich Boehm W Wenhui Huang S Shan Bian A Amit Agarwal M Marcel A. Lauterbach C Chenju Yi (Research Centre) J Jianqin Niu A Anja Scheller F Frank Kirchhoff (Institute of Molecular Virology, Ulm University Medical Center) X Xianshu Bai

Abstract

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published January 30, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (24)

L

Li-Pao Fang

C

Ching-Hsin Lin

Y

Yasser Medlej

R

Renping Zhao

H

Hsin-Fang Chang

Department of Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University

Q

Qilin Guo

Z

Zhonghao Wu

Y

Yixun Su

N

Na Zhao

D

Davide Gobbo

A

Amanda Wyatt

V

Vanessa Wahl

Max-Planck Institut für Molekulare Pflanzenphysiologie

F

Frederic Fiore

S

Szu-Min Tu

Department of Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University

U

Ulrich Boehm

W

Wenhui Huang

S

Shan Bian

A

Amit Agarwal

M

Marcel A. Lauterbach

C

Chenju Yi

Research Centre

J

Jianqin Niu

A

Anja Scheller

F

Frank Kirchhoff

Institute of Molecular Virology, Ulm University Medical Center

X

Xianshu Bai