Researchers from Institute of Genetics and Developmental Biology of Chinese Academy of Sciences generated mice with conditional knockout (cKO) of Mea6 in oligodendrocytes. Using different models of diffusion magnetic resonance imaging, the team reported “Ablation of Mea6/cTAGES in oligodendrocytes significantly impairs white matter structure and lipid content” in Life Metabolism that it detected the dramatically affected gross and microstructure of white matter, as well as its lipid and water diffusion capacity, in Mea6-cKO brains.

“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,” write the investigators.

Model for the function of Mea6 in oligodendrocytes. Mea6 is involved in the transport of different lipids from the ER to the Golgi apparatus and plays an essential role in the formation and/or maintenance of white matter. The conditional knockout of Mea6 in mice affects the composition of major myelin lipids, especially different VLCFAs, leading to the hypomyelination of axons. [Tiantian Ma, Wei Mao, Shaohua Zhang, Yaqing Wang, Tao Wang, Jinghua Liu, Lei Shi, Rong Xue, Guanghou Shui, Zhiheng Xu, Chinese Academy of Sciences]

“However, whether the impaired brain function involves the development of oligodendrocytes and white matter beyond neurons remains unclear [More than half of the adult human brain is made up of white matter].

“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 ).”

This 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, according to the researchers.

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