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

Roberto Angelini, Eylan Yutuc, Mark F. Wyatt, Jillian Newton, Fowzi A. Yusuf, Lauren Griffiths, Benjamin J. 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 W. Howell, Malcolm R. Clench, Yuqin Wang, William J. Griffiths

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4932-4943
Number of pages12
JournalAnalytical Chemistry
Volume93
Issue number11
DOIs
StatePublished - Mar 23 2021

ASJC Scopus subject areas

  • Analytical Chemistry

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