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Correlated heterospectral lipidomics for biomolecular profiling of remyelination in multiple sclerosis

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Title: Correlated heterospectral lipidomics for biomolecular profiling of remyelination in multiple sclerosis
Authors: Bergholt, MS
Serio, A
McKenzie, JS
Boyd, A
Soares, RF
Tillner, J
Chiappini, C
Wu, V
Dannhorn, A
Takats, Z
Williams, A
Stevens, MM
Item Type: Journal Article
Abstract: Analyzing lipid composition and distribution within the brain is important to study white matter pathologies that present focal demyelination lesions, such as multiple sclerosis. Some lesions can endogenously re-form myelin sheaths. Therapies aim to enhance this repair process in order to reduce neurodegeneration and disability progression in patients. In this context, a lipidomic analysis providing both precise molecular classification and well-defined localization is crucial to detect changes in myelin lipid content. Here we develop a correlated heterospectral lipidomic (HSL) approach based on coregistered Raman spectroscopy, desorption electrospray ionization mass spectrometry (DESI-MS), and immunofluorescence imaging. We employ HSL to study the structural and compositional lipid profile of demyelination and remyelination in an induced focal demyelination mouse model and in multiple sclerosis lesions from patients ex vivo. Pixelwise coregistration of Raman spectroscopy and DESI-MS imaging generated a heterospectral map used to interrelate biomolecular structure and composition of myelin. Multivariate regression analysis enabled Raman-based assessment of highly specific lipid subtypes in complex tissue for the first time. This method revealed the temporal dynamics of remyelination and provided the first indication that newly formed myelin has a different lipid composition compared to normal myelin. HSL enables detailed molecular myelin characterization that can substantially improve upon the current understanding of remyelination in multiple sclerosis and provides a strategy to assess remyelination treatments in animal models.
Issue Date: 27-Dec-2017
Date of Acceptance: 21-Nov-2017
URI: http://hdl.handle.net/10044/1/54031
DOI: https://dx.doi.org/10.1021/acscentsci.7b00367
ISSN: 2374-7943
Publisher: American Chemical Society
Start Page: 39
End Page: 51
Journal / Book Title: ACS Central Science
Volume: 4
Issue: 1
Copyright Statement: This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Sponsor/Funder: Medical Research Council (MRC)
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Commission of the European Communities
Commission of the European Communities
Funder's Grant Number: MR/K026666/1
305940
MR/L012677/1
MR/K026682/1
617896
701713
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
MASS-SPECTROMETRY
BIOLOGICAL TISSUE
MALDI-TOF
COLORECTAL-CANCER
MYELIN
RAMAN
BRAIN
MS
DEMYELINATION
SPECTROSCOPY
Publication Status: Published
Appears in Collections:Faculty of Engineering
Materials
Division of Surgery
Faculty of Medicine
Faculty of Natural Sciences



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