Lipid-rich myelin, a unique structure formed by oligodendrocytes wrapping around neuronal axons, comprises over half of the adult human brain’s white matter. An abnormal myelin sheath is linked to numerous neurological diseases. The findings were published in the journal Life Metabolism.
Meningioma-expressed antigen 6 (Mea6) and cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) play crucial roles in vesicle trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus. Conditional knockout (cKO) of Mea6 in the brain significantly impacts neural development and function. However, it remains unclear whether impaired brain function involves the development of oligodendrocytes and white matter beyond neurons.
In this study, scientists from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences generated mice with conditional knockout (cKO) of Mea6 in oligodendrocytes. Using various models of diffusion magnetic resonance imaging, the researchers found that the cKO of Mea6 in oligodendrocytes led to a significant impairment of white matter’s gross and microstructure, as well as a considerable decrease in cholesterol and triglycerides in the brain.
Their groundbreaking lipidomic analysis of purified myelin sheath revealed that Mea6 elimination in oligodendrocytes significantly altered the lipid composition of the myelin lipidome, particularly the proportion of very long-chain fatty acids (VLCFAs). Most notably, the levels of most VLCFA-containing phosphatidylcholines were substantially lower in the myelin sheath of cKO mice. The reduction of VLCFAs is likely due to the downregulated expression of elongation of very long-chain fatty acids proteins (ELOVLs).
The study, which focused on an animal model with white matter malformation and comprehensive lipid profiling, offers valuable insights for future research on myelin lipids and the pathogenesis of white matter diseases.