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Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model

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Abstract

Mass spectrometry imaging (MSI) is a powerful tool to perform untargeted mapping of biomolecules in situ. In the current study, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to evaluate lipid changes during disease progression (asymptomatic to symptomatic time points) in Niemann-Pick disease, type C1 (NPC1), a cerebellar neurodegenerative, lipid storage disorder. Our data show that gangliosides GM2 and GM3 are elevated in NPC1 disease and localize in the posterior lobules of the cerebellum, which is enhanced over a time-course analysis of the disease. Further analysis of sphingolipids in negative ion mode indicated reduction of sulfatides in white matter of the cerebellum and patterned distribution and co-localization of ceramide species Cer(d36:1), HexCer(d36:1), and the ganglioside GM1(d36:1) during disease progression. Finally, a putative lipid of unknown structure demonstrated similar patterning during NPC1 cerebellar degeneration. These studies provide insight into lipid markers of neurodegeneration in NPC1 and link lipid alterations to altered pathways that lead to cell death.

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Acknowledgments

The authors would like to acknowledge the support from the University of Illinois at Chicago, Department of Chemistry and College of Liberal Arts and Sciences, and the Ara Parseghian Medical Research Foundation.

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  1. Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor St., Chicago, IL, 60607, USA

    Fernando Tobias, Koralege C. Pathmasiri & Stephanie M. Cologna

  2. Laboratory for Integrative Neuroscience, University of Illinois at Chicago, 845 W. Taylor St., Chicago, IL, 60607, USA

    Stephanie M. Cologna

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Tobias, F., Pathmasiri, K.C. & Cologna, S.M. Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model. Anal Bioanal Chem 411, 5659–5668 (2019). https://doi.org/10.1007/s00216-019-01989-7

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