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

被引：40

作者：

Angelini, Roberto ^{[1
]}

Yutuc, Eylan ^{[1
]}

Wyatt, Mark F. ^{[1
]}

Newton, Jillian ^{[2
]}

Yusuf, Fowzi A. ^{[1
]}

Griffiths, Lauren ^{[1
]}

Cooze, Benjamin J. ^{[1
]}

El Assad, Dana ^{[3
]}

Frache, Gilles ^{[3
]}

Rao, Wei ^{[4
]}

Allen, Luke B. ^{[5
,6
]}

Korade, Zeljka ^{[5
,6
]}

Nguyen, Thu T. A. ^{[7
,8
]}

Rathnayake, Rathnayake A. C. ^{[7
,8
]}

Cologna, Stephanie M. ^{[7
,8
]}

Howell, Owain W. ^{[1
]}

Clench, Malcolm R. ^{[2
]}

Wang, Yuqin ^{[1
]}

Griffiths, William J. ^{[1
]}

机构：

[1] Swansea Univ, Med Sch, Swansea SA2 8PP, W Glam, Wales

[2] Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 IWB, S Yorkshire, England

[3] Luxembourg Inst Sci & Technol, Mat Res & Technol, L-4422 Belvaux, Luxembourg

[4] Waters Corp, European Applicat Lab, Wilmslow SK9 4AX, Cheshire, England

[5] Univ Nebraska Med Ctr, Dept Pediat, Omaha, NE 68198 USA

[6] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA

[7] Univ Illinois, Dept Chem, Chicago, IL 60607 USA

[8] Univ Illinois, Lab Integrated Neurosci, Chicago, IL 60607 USA

来源：

ANALYTICAL CHEMISTRY | 2021年 / 93卷 / 11期

基金：

英国生物技术与生命科学研究理事会;

关键词：

All Open Access; Hybrid Gold;

D O I：

10.1021/acs.analchem.0c05399

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

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.

引用

页码：4932 / 4943

页数：12

共 47 条

[1] Quantitative Spatial Analysis of the Mouse Brain Lipidome by Pressurized Liquid Extraction Surface Analysis [J].

Almeida, Reinaldo ;

Berzina, Zane ;

Arnspang, Eva C. ;

Baumgart, Jan ;

Vogt, Johannes ;

Nitsch, Robert ;

Ejsing, Christer S. .

ANALYTICAL CHEMISTRY, 2015, 87 (03) :1749-1756

[2] QuPath: Open source software for digital pathology image analysis [J].

Bankhead, Peter ;

Loughrey, Maurice B. ;

Fernandez, Jose A. ;

Dombrowski, Yvonne ;

Mcart, Darragh G. ;

Dunne, Philip D. ;

McQuaid, Stephen ;

Gray, Ronan T. ;

Murray, Liam J. ;

Coleman, Helen G. ;

James, Jacqueline A. ;

Salto-Tellez, Manuel ;

Hamilton, Peter W. .

SCIENTIFIC REPORTS, 2017, 7

[3] Enhanced Sensitivity Using MALDI Imaging Coupled with Laser Postionization (MALDI-2) for Pharmaceutical Research [J].

Barre, Florian P. Y. ;

Paine, Martin R. L. ;

Flinders, Bryn ;

Trevitt, Adam J. ;

Kelly, Patrick D. ;

Ait-Belkacem, Rima ;

Garcia, Joao P. ;

Creemers, Laura B. ;

Stauber, Jonathan ;

Vreeken, Rob J. ;

Cillero-Pastor, Berta ;

Ellis, Shane R. ;

Heeren, Ron M. A. .

ANALYTICAL CHEMISTRY, 2019, 91 (16) :10840-10848

[4] Derivatization Strategies for the Detection of Triamcinolone Acetonide in Cartilage by Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging [J].

Barre, Florian P. Y. ;

Flinders, Bryn ;

Garcia, Joao P. ;

Jansen, Imke ;

Huizing, Lennart R. S. ;

Porta, Tiffany ;

Creemers, Laura B. ;

Heeren, Ron M. A. ;

Cillero-Pastor, Berta .

ANALYTICAL CHEMISTRY, 2016, 88 (24) :12051-12059

[5] MALDI Imaging of Lipid Biochemistry in Tissues by Mass Spectrometry [J].

Berry, Karin A. Zemski ;

Hankin, Joseph A. ;

Barkley, Robert M. ;

Spraggins, Jeffrey M. ;

Caprioli, Richard M. ;

Murphy, Robert C. .

CHEMICAL REVIEWS, 2011, 111 (10) :6491-6512

[6] Genetic connections between neurological disorders and cholesterol metabolism [J].

Bjorkhem, Ingemar ;

Leoni, Valerio ;

Meaney, Steve .

JOURNAL OF LIPID RESEARCH, 2010, 51 (09) :2489-2503

[7] Target-specific contrast agents for magnetic resonance microscopy [J].

Blackwell, Megan L. ;

Farrar, Christian T. ;

Fischl, Bruce ;

Rosen, Bruce R. .

NEUROIMAGE, 2009, 46 (02) :382-393

[8] Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS [J].

Caprioli, RM ;

Farmer, TB ;

Gile, J .

ANALYTICAL CHEMISTRY, 1997, 69 (23) :4751-4760

[9] Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial [J].

Chataway, Jeremy ;

Schuerer, Nadine ;

Alsanousi, Ali ;

Chan, Dennis ;

MacManus, David ;

Hunter, Kelvin ;

Anderson, Val ;

Bangham, Charles R. M. ;

Clegg, Shona ;

Nielsen, Casper ;

Fox, Nick C. ;

Wilkie, David ;

Nicholas, Jennifer M. ;

Calder, Virginia L. ;

Greenwood, John ;

Frost, Chris ;

Nicholas, Richard .

LANCET, 2014, 383 (9936) :2213-2221

[10] Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues [J].

Cobice, Diego F. ;

Mackay, C. Logan ;

Goodwin, Richard J. A. ;

McBride, Andrew ;

Langridge-Smith, Patrick R. ;

Webster, Scott P. ;

Walker, Brian R. ;

Andrew, Ruth .

ANALYTICAL CHEMISTRY, 2013, 85 (23) :11576-11584

← 1 2 3 4 5 →