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

[Image: see text] 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 s...

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Autores principales: Angelini, Roberto, Yutuc, Eylan, Wyatt, Mark F., Newton, Jillian, Yusuf, Fowzi A., Griffiths, Lauren, Cooze, Benjamin J., El Assad, Dana, Frache, Gilles, Rao, Wei, Allen, Luke B., Korade, Zeljka, Nguyen, Thu T. A., Rathnayake, Rathnayake A. C., Cologna, Stephanie M., Howell, Owain W., Clench, Malcolm R., Wang, Yuqin, Griffiths, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992047/
https://www.ncbi.nlm.nih.gov/pubmed/33687199
http://dx.doi.org/10.1021/acs.analchem.0c05399
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author Angelini, Roberto
Yutuc, Eylan
Wyatt, Mark F.
Newton, Jillian
Yusuf, Fowzi A.
Griffiths, Lauren
Cooze, Benjamin J.
El Assad, Dana
Frache, Gilles
Rao, Wei
Allen, Luke B.
Korade, Zeljka
Nguyen, Thu T. A.
Rathnayake, Rathnayake A. C.
Cologna, Stephanie M.
Howell, Owain W.
Clench, Malcolm R.
Wang, Yuqin
Griffiths, William J.
author_facet Angelini, Roberto
Yutuc, Eylan
Wyatt, Mark F.
Newton, Jillian
Yusuf, Fowzi A.
Griffiths, Lauren
Cooze, Benjamin J.
El Assad, Dana
Frache, Gilles
Rao, Wei
Allen, Luke B.
Korade, Zeljka
Nguyen, Thu T. A.
Rathnayake, Rathnayake A. C.
Cologna, Stephanie M.
Howell, Owain W.
Clench, Malcolm R.
Wang, Yuqin
Griffiths, William J.
author_sort Angelini, Roberto
collection PubMed
description [Image: see text] 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.
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spelling pubmed-79920472021-03-25 Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging Angelini, Roberto Yutuc, Eylan Wyatt, Mark F. Newton, Jillian Yusuf, Fowzi A. Griffiths, Lauren Cooze, Benjamin J. El Assad, Dana Frache, Gilles Rao, Wei Allen, Luke B. Korade, Zeljka Nguyen, Thu T. A. Rathnayake, Rathnayake A. C. Cologna, Stephanie M. Howell, Owain W. Clench, Malcolm R. Wang, Yuqin Griffiths, William J. Anal Chem [Image: see text] 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. American Chemical Society 2021-03-09 2021-03-23 /pmc/articles/PMC7992047/ /pubmed/33687199 http://dx.doi.org/10.1021/acs.analchem.0c05399 Text en © 2021 The Authors. Published by American Chemical Society Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Angelini, Roberto
Yutuc, Eylan
Wyatt, Mark F.
Newton, Jillian
Yusuf, Fowzi A.
Griffiths, Lauren
Cooze, Benjamin J.
El Assad, Dana
Frache, Gilles
Rao, Wei
Allen, Luke B.
Korade, Zeljka
Nguyen, Thu T. A.
Rathnayake, Rathnayake A. C.
Cologna, Stephanie M.
Howell, Owain W.
Clench, Malcolm R.
Wang, Yuqin
Griffiths, William J.
Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
title 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_short 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
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992047/
https://www.ncbi.nlm.nih.gov/pubmed/33687199
http://dx.doi.org/10.1021/acs.analchem.0c05399
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