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Publication : Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse.

First Author  Meljon A Year  2014
Journal  Biochem Biophys Res Commun Volume  446
Issue  3 Pages  768-74
PubMed ID  24491562 Mgi Jnum  J:325508
Mgi Id  MGI:7285007 Doi  10.1016/j.bbrc.2014.01.153
Citation  Meljon A, et al. (2014) Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse. Biochem Biophys Res Commun 446(3):768-74
abstractText  Oxysterols are oxidised forms of cholesterol or its precursors. In this study we utilised the cholesterol 24-hydroxylase knockout mouse (Cyp46a1-/-) to study the sterol and oxysterol content of brain. Despite a great reduction in the abundance of 24S-hydroxycholesterol, the dominant metabolite of cholesterol in wild type brain, no other cholesterol metabolite was found to quantitatively replace this oxysterol in the Cyp46a1-/- mouse. Only minor amounts of other side-chain oxysterols including 22R-, 24R-, 25- and (25R),26-hydroxycholesterols were detected. In line with earlier studies, levels of cholesterol were similar in Cyp46a1-/- and wild type animals. However, the level of the cholesterol precursor, desomsterol, and its parallel metabolite formed via a shut of the mevalonate pathway, 24S,25-epoxycholesterol, were reduced in the Cyp46a1-/- mouse. The reduction in abundance of 24S,25-epoxycholesterol is interesting in light of a recent report indicating that this oxysterol promotes dopaminergic neurogenesis.
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