As OLs extend up to 60 myelinated processes and can generate up to 50 × 103 µm3 of membrane per day, myelination and remyelination are highly demanding processes. Up to 80% of myelin membrane is formed of lipids as main structural components, and the integration of cholesterol and fatty acids into myelin membranes is a critical aspect of myelin growth during development and remyelination102–104. For instance, cholesterol in oligodendrocytes is an essential building block for efficient myelin growth102. However, OLs do not solely rely on their own production of lipids for myelination. Conditional deletion of genes in OLs critical for lipid synthesis leads to reduced OL number and impaired myelination, yet these eventually normalize, indicating compensation through uptake from neighboring cells102,105. Indeed, astrocyte conditional knockouts which impair their lipid synthesis in development result in hypomyelination, and myelin defects only persist when both OL and astrocyte lipid synthesis are inhibited105. However, dietary lipid supplementation improves neurological deficits caused by the lack of lipid generation by astrocytes106.
