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Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism / Eylan, Yutuc; Roberto, Angelini; David, Skibinski; Owain, Howell; Yuqin, Wang; William, Griffiths

Proceedings of the National Academy of Sciences, Volume: 117, Issue: 11, Pages: 5749 - 5760

Swansea University Authors: Eylan, Yutuc, Roberto, Angelini, David, Skibinski, Owain, Howell, Yuqin, Wang, William, Griffiths

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Abstract

Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol...

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Published in: Proceedings of the National Academy of Sciences
ISSN: 0027-8424 1091-6490
Published: Proceedings of the National Academy of Sciences 2020
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa53792
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Abstract: Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatization in combination with microliquid extraction for surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400-µm spot diameter with a limit of quantification of 0.01 ng/mm2 It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-to-ionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type and cholesterol 24S-hydroxylase knockout mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.
Keywords: liquid chromatography-mass spectrometry, brain, cholesterol, 24Shydroxycholesterol, 24S,25-epoxycholesterol
Issue: 11
Start Page: 5749
End Page: 5760