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Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis.

TitleCorrelated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis.
Publication TypeJournal Article
Year of Publication2018
AuthorsBergholt MS, Serio A, McKenzie JS, Boyd A, Soares RF, Tillner J, Chiappini C, Wu V, Dannhorn A, Takats Z, Williams AC, Stevens MM
JournalACS Cent Sci
Volume4
Issue1
Pagination39-51
Date Published2018 Jan 24
ISSN2374-7943
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 . 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.

DOI10.1021/acscentsci.7b00367
Alternate JournalACS Cent Sci
PubMed ID29392175
PubMed Central IDPMC5785772
Grant ListMR/K026666/1 / / Medical Research Council / United Kingdom
MR/K026682/1 / / Medical Research Council / United Kingdom
MR/L012677/1 / / Medical Research Council / United Kingdom
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