title: Imaging mass spectrometry to visualize biomolecule distributions in mouse brain tissue following hemispheric cortical spreading depression.
abstract: MALDI mass spectrometry can simultaneously measure hundreds of biomolecules directly from tissue. Using essentially the same technique but different sample preparation strategies, metabolites, lipids, peptides and proteins can be analyzed. Spatially correlated analysis, imaging MS, enables the distributions of these biomolecular ions to be simultaneously measured in tissues. A key advantage of imaging MS is that it can annotate tissues based on their MS profiles and thereby distinguish biomolecularly distinct regions even if they were unexpected or are not distinct using established histological and histochemical methods e.g. neuropeptide and metabolite changes following transient electrophysiological events such as cortical spreading depression (CSD), which are spreading events of massive neuronal and glial depolarisations that occur in one hemisphere of the brain and do not pass to the other hemisphere , enabling the contralateral hemisphere to act as an internal control. A proof-of-principle imaging MS study, including 2D and 3D datasets, revealed substantial metabolite and neuropeptide changes immediately following CSD events which were absent in the protein imaging datasets. The large high dimensionality 3D datasets make even rudimentary contralateral comparisons difficult to visualize. Instead non-negative matrix factorization (NNMF), a multivariate factorization tool that is adept at highlighting latent features, such as MS signatures associated with CSD events, was applied to the 3D datasets. NNMF confirmed that the protein dataset did not contain substantial contralateral differences, while these were present in the neuropeptide dataset.
authors: Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands.
authors: Emrys A
authors: EA
authors: Jones
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors: Reinald
authors: R
authors: Shyti
authors: Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands.
authors: René J M
authors: RJM
authors: van Zeijl
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors: Sandra H
authors: SH
authors: van Heiningen
authors: Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
authors: Michel D
authors: MD
authors: Ferrari
authors: Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands.
authors: André M
authors: AM
authors: Deelder
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
authors: Else A
authors: EA
authors: Tolner
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
authors: Arn M J M
authors: AMJM
authors: van den Maagdenberg
authors: Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: l.a.mcdonnell@lumc.nl.
authors: Liam A
authors: LA
authors: McDonnell
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D003198:Computer Simulation; D013181:Cortical Spreading Depression / Q000502:physiology*; D003952:Diagnostic Imaging / Q000379:methods; D006651:Histocytochemistry / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014018:Tissue Distribution
chemical_list: D001685:Biological Factors; D010455:Peptides; D011506:Proteins