Ablation of Mea6/cTAGE5 in oligodendrocytes significantly impairs white matter structure and lipid content  

作　　者：Tiantian Ma Wei Mao Shaohua Zhang Yaqing Wang Tao Wang Jinghua Liu Lei Shi Xiang Yu Rong Xue Guanghou Shui Zhiheng Xu 

机构地区：[1]State Key Laboratory of Molecular Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China [2]State Key Laboratory of Brain and Cognitive Science,Beijing MRI Center for Brain Research,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]Sino-Danish College,University of Chinese Academy of Sciences,Beijing 100049,China [5]School of Life Sciences,Peking University,Beijing 100871,China [6]Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Beijing 100101,China [7]Beijing Institute for Brain Disorders,Collaborative Innovation Center for Brain Disorders,Capital Medical University,Beijing 100069,China

出　　处：《Life Metabolism》2023年第2期10-22,共13页生命（代谢（英文）

基　　金：This study was supported in part by grants from the National Natural Science Foundation of China(NSFC)(31921002,31730108,31730039,and 32061143026);Guangdong Province Key Field R&D Program(2018B030335001);Major Projects of the Ministry of Science and Technology(2021ZD0202300,2022ZD0211901,and 2019YFA0707103);the Strategic Priority Research Program and Innovation Program of the Chinese Academy of Sciences(XDB32020100,YJKYYQ20200052,and ZDBS-LY-SM028).

摘　　要：Lipid-rich myelin is a special structure formed by oligodendrocytes wrapping neuronal axons.Abnormal myelin sheath is associated with many neurological diseases.Meningioma-expressed antigen 6(Mea6)/cutaneous T cell lymphoma-associated antigen 5C(cTAGE5C)plays an important role in vesicle trafficking from the endoplasmic reticulum(ER)to Golgi,and conditional knockout(cKO)of Mea6 in the brain significantly affects neural development and brain function.However,whether the impaired brain function involves the development of oligodendrocytes and white matter beyond neurons remains unclear.In this study,by using different models of diffusion magnetic resonance imaging,we showed that cKO of Mea6 in oligodendrocytes leads to significant impairment of the gross and microstructure of the white matter,as well as a significant decrease of cholesterol and triglycerides in brains.Our lipidomic analysis of purified myelin sheath for the first time showed that Mea6 elimination in oligodendrocytes significantly altered the lipid composition in myelin lipidome,especially the proportion of very long chain fatty acids(VLCFAs).In particular,the levels of most VLCFA-containing phosphatidylcholines were substantially lower in the myelin sheath of the cKO mice.The reduction of VLCFAs is likely due to the downregulated expression of elongation of very long chain fatty acids(ELOVLs).Our study of an animal model with white matter malformation and the comprehensive lipid profiling would provide clues for future studies of the formation of myelin sheath,myelin lipids,and the pathogenesis of white matter diseases.

关 键 词：Mea6 OLIGODENDROCYTE HYPOMYELINATION myelin lipidomic analysis 

分 类 号：R741[医药卫生—神经病学与精神病学]