Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse |
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Authors: | Anna Meljon Yuqin WangWilliam J Griffiths |
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Institution: | Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK |
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Abstract: | 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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Keywords: | 24S-Hydroxycholesterol 24R-Hydroxycholesterol 24S 25-Epoxycholesterol Oxysterol Brain Cyp46a1 |
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