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 7α-hydroxydesmosterol were identified in brain for the first time.
Institute of Mass Spectrometry, College of Medicine, Swansea,  UK.
Anna
A
Meljon
Spyridon
S
Theofilopoulos
Cedric H L
CH
Shackleton
Gordon L
GL
Watson
Norman B
NB
Javitt
Hans-Joachim
HJ
Knölker
Ratni
R
Saini
Ernest
E
Arenas
Yuqin
Y
Wang
William J
WJ
Griffiths
D000818:Animals; D000831:Animals, Newborn; D002784:Cholesterol / Q000032:analysis; D002853:Chromatography, Liquid / Q000379:methods*; D003897:Desmosterol / Q000032:analysis; D006888:Hydroxycholesterols / Q000032:analysis; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D013261:Sterols / Q000032:analysis*
D006888:Hydroxycholesterols; D013261:Sterols; D003897:Desmosterol; D002784:Cholesterol