title: Spatial elucidation of spinal cord lipid- and metabolite- regulations in amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.
authors.affiliation: 1] National Center for Imaging Mass Spectrometry, University of Gothenburg and Chalmers University of Technology, Gothenburg, Sweden [2] Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hanrieder
authors.affiliation: 1] National Center for Imaging Mass Spectrometry, University of Gothenburg and Chalmers University of Technology, Gothenburg, Sweden [2] Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden [3] Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Ewing
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000870:Anterior Horn Cells / Q000378:metabolism; D016022:Case-Control Studies; D016923:Cell Death / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000502:physiology*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D016472:Motor Neuron Disease / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: D008055:Lipids; D008244:Lysophosphatidylcholines; D014280:Triglycerides; D014810:Vitamin E; D002784:Cholesterol