Autophagy in Oligodendrocyte Lineage Cells Controls Oligodendrocyte Numbers and Myelin Integrity in an Age-dependent Manner
Hong Chen1,2 · Gang Yang3 · De‑En Xu4 · Yu‑tong Du1,2 · Chao Zhu1,2 · Hua Hu1,2 · Li Luo5 · Lei Feng6 · Wenhui Huang7 · Yan‑Yun Sun1,2 · Quan‑Hong Ma1,21 Department of Neurology and Clinical Research Center of Neurological Disease, The Second Afliated 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
Abstract
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.
Keywords
Autophagy; Oligodendrocyte precursor cells; Oligodendrocytes; Myelination; Myelin proteins; Turnover; Degradation
