Reduced cholesterol alters the biophysical properties of repaired myelin
Year: 2025
Type: article
Abstract: The myelin sheath is a lipid-rich membrane that ensheathes axons and is required for healthy and efficient signal transduction. Myelin is damaged in neurological diseases like multiple sclerosis, but remyelination can occur through the action of oligodendrocyte precursor cells (OPCs), which differentiate into mature oligodendrocytes that wrap axons to form repaired myelin. In this study, a genetic-based mouse model of demyelination was used, which features near-complete demyelination followed by robust remyelination in the brain. Lipid mass spectrometry on isolated myelin from the remyelinated brain revealed a decrease in the percent mole fraction of cholesterol when compared to healthy myelin. Biophysical studies on monomolecular lipid films formed using repaired myelin lipid extracts showed changes in the surface behavior of the lipid films, compared to the healthy myelin lipids. Films formed using the remyelinated lipid extracts resulted in lower surface pressures and lower compressional moduli when compared to healthy controls, suggesting that repaired myelin membranes have lower lateral molecular packing within the lipid film. Synthetically prepared model membranes, based on the major lipid compositions of the healthy and diseased extracts, revealed that changes in cholesterol levels were the primary contributor to the changes in biophysical properties. Supplementation of the diseased lipid extracts with cholesterol led to a robust improvement in membrane surface pressures and compressibility. Together, these results suggest that high cholesterol levels are required for myelin membrane stability and that reduced cholesterol in repaired myelin may have a profound impact on the biophysical properties of the myelin membrane.
Institution: University of Kansas
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,670
Funders: National Science Foundation, U.S. Department of Agriculture, National Multiple Sclerosis Society, Kansas State University, Fulbright Association, Kentucky IDeA Networks of Biomedical Research Excellence, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, National Institutes of Health, National Institute of Food and Agriculture, National Institute of General Medical Sciences
Awards: G2972030790, G5054411426, MRI: Acquisition of an electrospray ionization triple quadrupole mass spectrometer with ion mobility spectrometry for improved plant lipidomics, Molecular Analysis of Disease Pathways, Kansas IDeA Network of Biomedical Research Excellence 5, Leveraging Big Data to Improve Women's Health (BD-WH)
OpenAlex ID: W4410529790