title: MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.
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 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. 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.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Germany.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Maccarrone
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nischwitz
authors.affiliation: Bruker Daltonik GmbH, Fahrenheitstr. 4, 28359 Bremen, Germany.
authors.forename: Sören-Oliver
authors.initials: SO
authors.lastname: Deininger
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hornung
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany; Institut für Pathologie, Klinikum Kassel, Mönchebergstr. 41-43, 34125 Kassel, Germany.
authors.forename: Fatima Barbara
authors.initials: FB
authors.lastname: König
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany; Medical Park Bad Camberg, Obertorstr. 100-102, 65520 Bad Camberg, Germany. Electronic address: fweber@psych.mpg.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010865:Pilot Projects; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013947:Thymosin / Q000032:analysis; D000099201:Thymosin beta(4)
chemical_list: D015415:Biomarkers; D011506:Proteins; D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: Demyelination; LC–ESI–MS/MS; MALDI imaging mass spectrometry; Multiple sclerosis; Remyelination; Thymosin beta-4