Autophagy in Oligodendrocyte Lineage Cells Controls Oligodendrocyte Numbers and Myelin Integrity in an Age‑dependent Manner  

作　　者：Hong Chen Gang Yang De‑En Xu Yu‑tong Du Chao Zhu Hua Hu Li Luo Lei Feng Wenhui Huang Yan‑Yun Sun Quan‑Hong Ma 

机构地区：[1]Department of Neurology and Clinical Research Center of Neurological Disease,The Second Affiliated Hospital of Soochow University,Suzhou 215004,China [2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience,Soochow University,Suzhou 215123,China [3]Lab Center,Medical College of Soochow University,Suzhou 215021,China [4]The Wuxi No.2 People Hospital,Wuxi 214002,China [5]School of Physical Education and Sports Science,Soochow University,Suzhou 215021,China [6]Monash Suzhou Research Institute,Suzhou 215000,China [7]Molecular Physiology,Center for Integrative Physiology and Molecular Medicine,University of Saarland,66421 Homburg,Germany

出　　处：《Neuroscience Bulletin》2025年第3期374-390,共17页神经科学通报(英文版)

基　　金：supported by the STI2030-Major Projects(2021ZD0204001);the National Natural Science Foundation of China(92049120,81870897,81271424,81671111,and 62475179);the Sino German Cooperation and Exchange Project(M-0679);the Guangdong Key Project in the Development of New Tools for the Diagnosis and Treatment of Autism(2018B030335001);the Natural Science Foundation of Jiangsu Province(BK20181436);the Priority Academic Program Development of Jiangsu Higher Education Institutions,the Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases(BM2013003);Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,Suzhou Science and Technology Plan Medical and Health Care Science and Technology Innovation Applied Basic Research(SKY2022161);the Research Project of Neurological Diseases in the Second Affiliated Hospital of Soochow University Research Center(ND2023A01);Boxi clinical research project of The First Affiliated Hospital of Soochow University(BXQN202204);Suzhou Science&Technology Projects for People's Livelihood(SKY2021065);Wuxi Municipal Health Commission(M202204).

摘　　要：Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.

关 键 词：AUTOPHAGY Oligodendrocyte precursor cells OLIGODENDROCYTES MYELINATION Myelin proteins Turnover Degradation 

分 类 号：R741[医药卫生—神经病学与精神病学]