Mea6 elimination in oligodendrocytes impairs white matter structure and lipid content

More than half amount in adult human brain is made up of white matter. Lipid-rich myelin is a special structure formed by oligodendrocytes wrapping neuronal axons to form the major components of white matter. Abnormal myelin sheath is associated with many neurological diseases. Mea6/ cTAGE5C is essential for vesicle trafficking from ER to Golgi. However, its biological function in oligodendrocyte and white matter development remains unclear.

Scientists 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, they detected the dramatically affected gross and microstructure of white matter, as well as its lipid and water diffusion capacity, in Mea6-cKO brains. A significant decrease in whole-brain cholesterol and triglycerides was detected in cKOs. In addition, they performed the first lipidomic analysis of purified myelin sheath and found that Mea6 elimination significantly altered the proportion of lipid components in myelin lipidome, especially very long-chain fatty acids (VLCFAs).

In particular, the levels of most VLCFA-containing phosphatidylcholines were significantly lower in cKOs. The reduction of VLCFAs is likely due to the reduced expression of ELOVLs (elongation of very long chain fatty acids proteins). This study entitled "Ablation of Mea6/cTAGE5 in oligodendrocytes significantly impairs white matter structure and lipid content" is published on 23 March 2023 online in Life Metabolism.

This study of an animal model with white matter malformation and the comprehensive lipid profiling would provide clues for future studies of myelin lipids and new insight into the pathogenesis of white matter diseases.