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MALDI imaging mass spectrometry, LC-BSI-MS/MS, Multiple Sclerosis, Demyelineation, Remyelineation, Thymosin beta-4
Abstract:
Multiple sclerosis is a disease of the central nervous system
characterized by recurrent inflammatory demyelinating lesions in the
early disease stage. Lesion formation and mechanisms leading to lesion
remyelination are not fully understood. Matrix Assisted Laser Desorption
Ionisation Mass Spectrometry imaging (MALDI IMS) is a technology which
analyses proteins and peptides in tissue, preserves their spatial
localization, and generates molecular maps within the tissue section. In
a pilot study we employed MALDI imaging mass spectrometry to profile and
identify peptides and proteins expressed in normal-appearing white
matter, grey matter and multiple sclerosis brain lesions with different
extents of remyelination. The unsupervised clustering analysis of the
mass spectra generated images which reflected the tissue section
morphology in luxol fast blue stain and in myelin basic protein
immunohistochemistry. Lesions with low remyelination extent were defined
by compounds with molecular weight smaller than 5300 Da, while more
completely remyelinated lesions showed compounds with molecular weights
greater than 15,200 Da. An in-depth analysis of the mass spectra enabled
the detection of cortical lesions which were not seen by routine luxol
fast blue histology. An ion mass, mainly distributed at the rim of
multiple sclerosis lesions, was identified by liquid chromatography and
tandem mass spectrometry as thymosin beta-4, a protein known to be
involved in cell migration and in restorative processes. The ion mass of
thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain
slides of 12 multiple sclerosis patients and validated by
immunohistochemical analysis. In summary, our results demonstrate the
ability of the MALDI IMS technology to map proteins within the brain
parenchyma and multiple sclerosis lesions and to identify potential
markers involved in multiple sclerosis pathogenesis and/or
remyelination. (C) 2016 Elsevier B.V. All rights reserved.
