Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
| Autor: | Dana El Assad, Malcolm R. Clench, Thu T A Nguyen, Mark F. Wyatt, Fowzi Adam Yusuf, Jillian Newton, Benjamin Jordan Cooze, Luke B. Allen, Owain W. Howell, Wei Rao, Zeljka Korade, Gilles Frache, William J. Griffiths, Yuqin Wang, Eylan Yutuc, Rathnayake A C Rathnayake, Lauren Griffiths, Stephanie M. Cologna, Roberto Angelini |
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| Rok vydání: | 2021 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities 010402 general chemistry Corpus callosum 01 natural sciences Mass Spectrometry Article Mass spectrometry imaging Analytical Chemistry Mice chemistry.chemical_compound medicine Animals Derivatization Cholesterol 010401 analytical chemistry Brain nutritional and metabolic diseases Niemann-Pick Disease Type C medicine.disease Sterol Pons 0104 chemical sciences Sterols chemistry Biochemistry lipids (amino acids peptides and proteins) NPC1 Niemann–Pick disease |
| Zdroj: | Analytical Chemistry |
| ISSN: | 1520-6882 0003-2700 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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