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

• Main Authors: Anna Meljon, Spyridon Theofilopoulos, Cedric H.L. Shackleton, Gordon L. Watson, Norman B. Javitt, Hans-Joachim Knölker, Ratni Saini, Ernest Arenas, Yuqin Wang, William J. Griffiths
• Format: Article
• Language: English
• Published: Elsevier 2012-11-01
• Series: Journal of Lipid Research
• Subjects: sterol; liver X receptor; desmosterol; cholesterol; 24S-hydroxycholesterol; 24S,25-epoxycholesterol
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520412647

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 C21-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 7α-hydroxydesmosterol were identified in brain for the first time