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

Fernando Tobias; Koralege C. Pathmasiri; Stephanie M. Cologna

doi:10.1007/s00216-019-01989-7

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

Fernando Tobias, Koralege C. Pathmasiri, Stephanie M. Cologna^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English (US)
Pages (from-to)	5659-5668
Number of pages	10
Journal	Analytical and Bioanalytical Chemistry
Volume	411
Issue number	22
DOIs	https://doi.org/10.1007/s00216-019-01989-7
State	Published - Sep 1 2019

Funding

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.

Keywords

Apoptosis
Ceramide
Cholesterol
Ganglioside
MALDI mass spectrometry imaging
Niemann-pick disease type C

ASJC Scopus subject areas

Analytical Chemistry
Biochemistry

Access to Document

10.1007/s00216-019-01989-7

Cite this

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

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.",

keywords = "Apoptosis, Ceramide, Cholesterol, Ganglioside, MALDI mass spectrometry imaging, Niemann-pick disease type C",

author = "Fernando Tobias and Pathmasiri, {Koralege C.} and Cologna, {Stephanie M.}",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2019, Springer-Verlag GmbH Germany, part of Springer Nature.",

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N1 - Funding Information: 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. Publisher Copyright: © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

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N2 - 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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