Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging

Angelini, Roberto; Yutuc, Eylan; Wyatt, Mark; Newton, Jillian; YUSUF, FOWZI; Griffiths, Lauren; Cooze, Benjamin; Assad, Dana El; Frache, Gilles; Rao, Wei; Allen, Luke B.; Korade, Zeljka; A., Thu T.; C., Rathnayake A.; Cologna, Stephanie M.; Howell, Owain; Clench, Malcolm R.; Wang, Yuqin; Griffiths, William

doi:10.1021/acs.analchem.0c05399

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Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging

Roberto Angelini

, Eylan Yutuc

, Mark Wyatt

, Jillian Newton, FOWZI YUSUF, Lauren Griffiths

, Benjamin Cooze, Dana El Assad, Gilles Frache, Wei Rao, Luke B. Allen, Zeljka Korade, Thu T. A. Nguyen, Rathnayake A. C. Rathnayake, Stephanie M. Cologna, Owain Howell

, Malcolm R. Clench, Yuqin Wang

, William Griffiths

Analytical Chemistry, Volume: 93, Issue: 11, Pages: 4932 - 4943

Swansea University Authors: Roberto Angelini , Eylan Yutuc , Mark Wyatt , FOWZI YUSUF, Lauren Griffiths , Benjamin Cooze, Owain Howell , Yuqin Wang , William Griffiths

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DOI (Published version): 10.1021/acs.analchem.0c05399

Abstract

Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve...

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Published in:	Analytical Chemistry
ISSN:	0003-2700 1520-6882
Published:	American Chemical Society (ACS) 2021
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa56326
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first_indexed	2021-03-12T13:04:17Z
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In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and during brain development. MSI revealed that in the adult mouse, cholesterol is the highest in the pons and medulla and how its distribution changes during development. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. 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spelling	2022-10-27T15:16:21.9759956 v2 56326 2021-02-25 Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging 6405b7880498750d41c93c6ff89cff96 0000-0001-5136-5921 Roberto Angelini Roberto Angelini true false 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false 7bd242b8bee1030a538b429c99913a7d 0000-0003-4107-5941 Mark Wyatt Mark Wyatt true false e7f9cdaa304f173e218c956605a8d2f2 FOWZI YUSUF FOWZI YUSUF true false 8811c280da03bf66352d97f756e91ae1 0000-0002-8713-3687 Lauren Griffiths Lauren Griffiths true false 785346ffc3dae14c560e63727f4017d3 Benjamin Cooze Benjamin Cooze 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 2021-02-25 BMS Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and during brain development. MSI revealed that in the adult mouse, cholesterol is the highest in the pons and medulla and how its distribution changes during development. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience. Journal Article Analytical Chemistry 93 11 4932 4943 American Chemical Society (ACS) 0003-2700 1520-6882 Mass spectrometry, Central nervous system, Steroids, Cholesterol, Rodent models 23 3 2021 2021-03-23 10.1021/acs.analchem.0c05399 http://dx.doi.org/10.1021/acs.analchem.0c05399 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University UKRI, BB/N015932/1 2022-10-27T15:16:21.9759956 2021-02-25T16:52:39.8071524 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Roberto Angelini 0000-0001-5136-5921 1 Eylan Yutuc 0000-0001-9971-1950 2 Mark Wyatt 0000-0003-4107-5941 3 Jillian Newton 4 FOWZI YUSUF 5 Lauren Griffiths 0000-0002-8713-3687 6 Benjamin Cooze 7 Dana El Assad 8 Gilles Frache 9 Wei Rao 10 Luke B. Allen 11 Zeljka Korade 12 Thu T. A. Nguyen 13 Rathnayake A. C. Rathnayake 14 Stephanie M. Cologna 15 Owain Howell 0000-0003-2157-9157 16 Malcolm R. Clench 17 Yuqin Wang 0000-0002-3063-3066 18 William Griffiths 0000-0002-4129-6616 19 56326__19468__46486b2304ff4cb5b182069bd83550e6.pdf 56326.pdf 2021-03-10T17:25:51.0270498 Output 7687859 application/pdf Version of Record true Released under the terms of a Creative Commons Attribution License (CC-BY) true eng https://creativecommons.org/licenses/by/4.0/
title	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
spellingShingle	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging Roberto Angelini Eylan Yutuc Mark Wyatt FOWZI YUSUF Lauren Griffiths Benjamin Cooze Owain Howell Yuqin Wang William Griffiths
title_short	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
title_full	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
title_fullStr	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
title_full_unstemmed	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
title_sort	Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
author_id_str_mv	6405b7880498750d41c93c6ff89cff96 99332f073ce913a9b7d8b6441b17516d 7bd242b8bee1030a538b429c99913a7d e7f9cdaa304f173e218c956605a8d2f2 8811c280da03bf66352d97f756e91ae1 785346ffc3dae14c560e63727f4017d3 58c995486fc93a242b987640b692db8c c92729b58622f9fdf6a0e7d8f4ce5081 3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv	6405b7880498750d41c93c6ff89cff96_*_Roberto Angelini 99332f073ce913a9b7d8b6441b17516d__Eylan Yutuc 7bd242b8bee1030a538b429c99913a7d__Mark Wyatt e7f9cdaa304f173e218c956605a8d2f2__FOWZI YUSUF 8811c280da03bf66352d97f756e91ae1__Lauren Griffiths 785346ffc3dae14c560e63727f4017d3__Benjamin Cooze 58c995486fc93a242b987640b692db8c__Owain Howell c92729b58622f9fdf6a0e7d8f4ce5081__Yuqin Wang 3316b1d1b524be1831790933eed1c26e_**_William Griffiths
author	Roberto Angelini Eylan Yutuc Mark Wyatt FOWZI YUSUF Lauren Griffiths Benjamin Cooze Owain Howell Yuqin Wang William Griffiths
author2	Roberto Angelini Eylan Yutuc Mark Wyatt Jillian Newton FOWZI YUSUF Lauren Griffiths Benjamin Cooze Dana El Assad Gilles Frache Wei Rao Luke B. Allen Zeljka Korade Thu T. A. Nguyen Rathnayake A. C. Rathnayake Stephanie M. Cologna Owain Howell Malcolm R. Clench Yuqin Wang William Griffiths
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container_title	Analytical Chemistry
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container_issue	11
container_start_page	4932
publishDate	2021
institution	Swansea University
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doi_str_mv	10.1021/acs.analchem.0c05399
publisher	American Chemical Society (ACS)
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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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
url	http://dx.doi.org/10.1021/acs.analchem.0c05399
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description	Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and during brain development. MSI revealed that in the adult mouse, cholesterol is the highest in the pons and medulla and how its distribution changes during development. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience.
published_date	2021-03-23T04:11:12Z
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Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging

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