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

Roberto Angelini Orcid Logo, Eylan Yutuc Orcid Logo, Mark Wyatt Orcid Logo, Jillian Newton, FOWZI YUSUF, Lauren Griffiths Orcid Logo, 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 Orcid Logo, Malcolm R. Clench, Yuqin Wang Orcid Logo, William Griffiths Orcid Logo

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

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

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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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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 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.
Keywords: Mass spectrometry, Central nervous system, Steroids, Cholesterol, Rodent models
College: Swansea University Medical School
Funders: UKRI, BB/N015932/1
Issue: 11
Start Page: 4932
End Page: 4943