Analysis of bioactive oxysterols in newborn mouse brain by LC/MS

Unesterified cholesterol is a major component of plasma membranes. In the brain of the adult, it is mostly found in myelin sheaths, where it plays a major architectural role. In the newborn mouse, little myelination of neurons has occurred, and much of this sterol comprises a metabolically active pool. In the current study, we have accessed this metabolically active pool and, using LC/MS, have identified cholesterol precursors and metabolites. Although desmosterol and 24S-hydroxycholesterol represent the major precursor and metabolite, respectively, other steroids, including the oxysterols 22-oxocholesterol, 22R-hydroxycholesterol, 20R, 22R-dihydroxycholesterol, and the C-21-neurosteroid progesterone, were identified. 24S, 25-epoxycholesterol formed in parallel to cholesterol was also found to be a major sterol in newborn brain. Like 24S- and 22R-hydroxycholesterols, and also desmosterol, 24S, 25-epoxycholesterol is a ligand to the liver X receptors, which are expressed in brain. The desmosterol metabolites (24Z), 26-, (24E), 26-, and 7 alpha- hydroxydesmosterol were identified in brain for the first time.-Meljon, A., S. Theofilopoulos, C. H. L. Shackleton, G. L. Watson, N. B. Javitt, H-J. Knolker, R. Saini, E. Arenas, Y. Wang, and W. J. Griffiths. Analysis of bioactive oxysterols in newborn mouse brain by LC/MS. J. Lipid Res. 2012. 53: 2469-2483.