Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

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YUTUC, Eylan, ANGELINI, Roberto, BAUMERT, Mark, MAST, Natalia, PIKULEVA, Irina, NEWTON, Jillian, CLENCH, Malcolm, SKIBINSKI, David O.F., HOWELL, Owain W., WANG, Yuqin and GRIFFITHS, William J. (2020). Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism. Proceedings of the National Academy of Sciences, p. 201917421. [Article]

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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.
More Information
Official URL:
https://www.pnas.org/content/early/2020/03/03/1917...
Page Range:
p. 201917421

Identifiers

Identification Number:
10.1073/pnas.1917421117
ORCID for Eylan Yutuc: ORCID iD orcid.org/0000-0001-9971-1950
ORCID for Roberto Angelini: ORCID iD orcid.org/0000-0001-5136-5921
ORCID for Natalia Mast: ORCID iD orcid.org/0000-0001-6427-640X
ORCID for Irina Pikuleva: ORCID iD orcid.org/0000-0001-9742-6232
ORCID for Malcolm Clench: ORCID iD orcid.org/0000-0002-0798-831X
ORCID for David O.F. Skibinski: ORCID iD orcid.org/0000-0003-4077-6236
ORCID for Owain W. Howell: ORCID iD orcid.org/0000-0003-2157-9157
ORCID for Yuqin Wang: ORCID iD orcid.org/0000-0002-3063-3066
ORCID for William J. Griffiths: ORCID iD orcid.org/0000-0002-4129-6616

Library

Item Type:
Article
SWORD Depositor:
Symplectic Elements
Depositing User:
Symplectic Elements
Date Deposited:
09 Mar 2020 16:51
Last Modified:
18 Dec 2024 22:00
Date of first compliant deposit:
9 March 2020
Date of first compliant Open Access:
9 March 2020
Version of first compliant deposit:
Version of Record
URI:
https://shura.shu.ac.uk/id/eprint/25950
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