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

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

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)2469-83
Number of pages15
JournalJournal of Lipid Research
Volume53
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Keywords

  • Animals
  • Animals, Newborn
  • Cholesterol/analysis
  • Chromatography, Liquid/methods
  • Desmosterol/analysis
  • Hydroxycholesterols/analysis
  • Mass Spectrometry/methods
  • Mice
  • Sterols/analysis

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