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

Eylan Yutuc Orcid Logo, Roberto Angelini Orcid Logo, Mark Baumert, Natalia Mast, Irina Pikuleva, Jillian Newton, Malcolm R. Clench, David Skibinski Orcid Logo, Owain Howell Orcid Logo, Yuqin Wang Orcid Logo, William Griffiths Orcid Logo

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

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

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DOI (Published version): 10.1073/pnas.1917421117

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
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URI: https://cronfa.swan.ac.uk/Record/cronfa53792
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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 &#xB5;m) of mouse brain. The method provides sterolomic analysis at 400-&#xB5;m 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. 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spelling 2020-09-21T15:52:46.1181247 v2 53792 2020-03-09 Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false 6405b7880498750d41c93c6ff89cff96 0000-0001-5136-5921 Roberto Angelini Roberto Angelini true false 328d16903f98c2b03a1cc64a7530322a 0000-0003-4077-6236 David Skibinski David Skibinski true false 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2020-03-09 BMS 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. Journal Article Proceedings of the National Academy of Sciences 117 11 5749 5760 Proceedings of the National Academy of Sciences 0027-8424 1091-6490 liquid chromatography-mass spectrometry, brain, cholesterol, 24Shydroxycholesterol, 24S,25-epoxycholesterol 17 3 2020 2020-03-17 10.1073/pnas.1917421117 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University UKRI, BB/N015932/1 2020-09-21T15:52:46.1181247 2020-03-09T16:26:45.0375724 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Eylan Yutuc 0000-0001-9971-1950 1 Roberto Angelini 0000-0001-5136-5921 2 Mark Baumert 3 Natalia Mast 4 Irina Pikuleva 5 Jillian Newton 6 Malcolm R. Clench 7 David Skibinski 0000-0003-4077-6236 8 Owain Howell 0000-0003-2157-9157 9 Yuqin Wang 0000-0002-3063-3066 10 William Griffiths 0000-0002-4129-6616 11 53792__16817__111b974079a3460bb0927a4d5ca761be.pdf Yutuc PNAS 2020.pdf 2020-03-10T08:43:58.4799384 Output 2666851 application/pdf Version of Record true Distributed under the terms of a Creative Commons Attribution Licence 4.0 (CC-BY) true eng http://creativecommons.org/licenses/by/4.0/
title Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
spellingShingle 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
title_short Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
title_full Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
title_fullStr Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
title_full_unstemmed Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
title_sort Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
author_id_str_mv 99332f073ce913a9b7d8b6441b17516d
6405b7880498750d41c93c6ff89cff96
328d16903f98c2b03a1cc64a7530322a
58c995486fc93a242b987640b692db8c
c92729b58622f9fdf6a0e7d8f4ce5081
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author_id_fullname_str_mv 99332f073ce913a9b7d8b6441b17516d_***_Eylan Yutuc
6405b7880498750d41c93c6ff89cff96_***_Roberto Angelini
328d16903f98c2b03a1cc64a7530322a_***_David Skibinski
58c995486fc93a242b987640b692db8c_***_Owain Howell
c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang
3316b1d1b524be1831790933eed1c26e_***_William Griffiths
author Eylan Yutuc
Roberto Angelini
David Skibinski
Owain Howell
Yuqin Wang
William Griffiths
author2 Eylan Yutuc
Roberto Angelini
Mark Baumert
Natalia Mast
Irina Pikuleva
Jillian Newton
Malcolm R. Clench
David Skibinski
Owain Howell
Yuqin Wang
William Griffiths
format Journal article
container_title Proceedings of the National Academy of Sciences
container_volume 117
container_issue 11
container_start_page 5749
publishDate 2020
institution Swansea University
issn 0027-8424
1091-6490
doi_str_mv 10.1073/pnas.1917421117
publisher Proceedings of the National Academy of Sciences
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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.
published_date 2020-03-17T04:06:55Z
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