TY - JOUR
T1 - Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging
AU - Angelini, Roberto
AU - Yutuc, Eylan
AU - Wyatt, Mark F.
AU - Newton, Jillian
AU - Yusuf, Fowzi A.
AU - Griffiths, Lauren
AU - Cooze, Benjamin J.
AU - El Assad, Dana
AU - Frache, Gilles
AU - Rao, Wei
AU - Allen, Luke B.
AU - Korade, Zeljka
AU - Nguyen, Thu T.A.
AU - Rathnayake, Rathnayake A.C.
AU - Cologna, Stephanie M.
AU - Howell, Owain W.
AU - Clench, Malcolm R.
AU - Wang, Yuqin
AU - Griffiths, William J.
N1 - Funding Information:
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC, grant numbers BB/N015932/1 to W.J.G./Y.W./O.W.H./M.R.C./J.N. and BB/L001942/1 to Y.W.). R.A. holds an MSCA-COFUND Sêr Cymru fellowship supported by the Welsh Government and the European Regional Development Fund. Work at the Nebraska Medical Center was supported by the NIH NIMH MH110636 (National Institute of Health National Institute of Mental Health). Work at the University of Illinois at Chicago was supported by the Ara Parseghian Medical Research Fund and the Department of Chemistry, College of Liberal Arts and Sciences. Dr Ruth Andrew (University of Edinburgh) is thanked for advice on performing on-tissue derivatization. We acknowledge Dr Rosalind John and Bridget Allen for kindly providing brains of CD1 mice (Cardiff University). Dr Tina Angerer (Luxembourg Institute of Science and Technology) is thanked for helpful discussions. We are grateful to Professor David O.F. Skibinsky (Swansea University) for providing statistical advice. R.A. dedicates this article to the memory of Detcho A. Stoyanovsky, a wonderful mentor and a great friend.
Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/3/23
Y1 - 2021/3/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103437324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103437324&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.0c05399
DO - 10.1021/acs.analchem.0c05399
M3 - Article
C2 - 33687199
AN - SCOPUS:85103437324
VL - 93
SP - 4932
EP - 4943
JO - Analytical Chemistry
JF - Analytical Chemistry
SN - 0003-2700
IS - 11
ER -