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

  title={Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model},
  author={Fernando Tobias and Koralege C. Pathmasiri and Stephanie M. Cologna},
  journal={Analytical and Bioanalytical Chemistry},
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… 

Mass spectrometry imaging and LC/MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice[S]

Significant depletion of multiple phosphoinositide species, including PI, PIP, and PIP2, in the cerebellum of the Npc1-null mice in both whole-tissue lysates and myelin-enriched fractions are suggested.

MALDI TIMS IMS of Disialoganglioside Isomers – GD1a and GD1b in Murine Brain Tissue

The gas-phase separation of disialoganglioside isomers GD1a and GD1b that differ in the position of a sialic acid residue is demonstrated, in a standard mixture of both isomers, a total gangliosides extract, and directly from thin tissue sections.

Elevation of gangliosides in four brain regions from Parkinson’s disease patients with a GBA mutation

It is concluded that changes in ganglioside, but not in GlcCer levels, may contribute to the association between PD and GBA mutations.

Identification of key molecular biomarkers involved in reactive and neurodegenerative processes present in inherited congenital hydrocephalus

The results identify possible biomarkers of hydrocephalus in the cerebral grey and white matter that could be reacting to acquire a neuroprotective role or as a delay in the oligodendrocyte maturation.

Brain region‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer’s disease mice

High‐spatial resolution matrix‐assisted laser desorption/ionization imaging mass spectrometry study in combination with (immuno) fluorescence staining of 5xFAD mouse brain provides new understanding of morphological, molecular and immune signatures of Aβ plaque pathology‐associated myelin lipid loss and myelin degeneration in a brain region‐specific manner.

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Evidence gathered so far indicates that purine receptors are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s and Niemann–Pick C diseases, by controlling the brain cholesterol homeostasis; in addition, alterations in cholesterol turnover can hinder the purine receptor function.

Considerations for MALDI-based Quantitative Mass Spectrometry Imaging Studies.

This work shares insights into sample preparation, how the choice of matrix influences sensitivity, construction of calibration curves, signal normalization, and visualization of MSI data, and hopes that by articulating these guidelines that qMSI can be routinely conducted while retaining the analytical merits of other mass spectrometry modalities.

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2017-2018.

  • D. Harvey
  • Chemistry
    Mass spectrometry reviews
  • 2021
MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress, with increasing use of combined new techniques such as ion mobility.

Developing a Drug Screening Platform: MALDI-Mass Spectrometry Imaging of Paper-Based Cultures.

The potential of matrix-assisted laser desorption/ionization - mass spectrometry imaging with PBCs (MALDI-MSI-PBC) as a drug screening platform is demonstrated, indicating that coupling P BCs with MALDI- MSI has the potential to develop rapid, large-scale, and parallel mass spectromaetric drug screens.

The rapidly evolving view of lysosomal storage diseases

It is now clear that substrate accumulation triggers complex pathogenetic cascades that are responsible for disease pathology, such as aberrant vesicle trafficking, impairment of autophagy, dysregulation of signaling pathways, abnormalities of calcium homeostasis, and mitochondrial dysfunction.



Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1[S]

This work uses MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls and demonstrates a universal approach for addressing reproducibility in imaging experiments applied to NPC1.

Quantitative, Label‐Free Proteomics in the Symptomatic Niemann–Pick, Type C1 Mouse Model Using Standard Flow Liquid Chromatography and Thermal Focusing Electrospray Ionization

In this study, alterations are observed in proteins related to fatty acid homeostasis, calcium binding and regulation, lysosomal regulation, and inositol biosynthesis and metabolism, as well as signaling by Rho family GTPases.

Identification of Niemann-Pick C1 disease biomarkers through sphingolipid profiling

Using targeted metabolomics to exploit the complex lipid storage phenotype that is the hallmark of NPC1 disease, broadly surveyed Npc1−/− mouse tissues and identified elevated species across multiple sphingolipid classes that increased with disease progression, suggesting lipid biomarkers may prove useful as outcome measures for monitoring efficacy of therapy in clinical trials.

Complex lipid trafficking in Niemann-Pick disease type C

  • M. Vanier
  • Biology, Chemistry
    Journal of Inherited Metabolic Disease
  • 2014
A reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models is provided, with emphasis on differences between systemic organs and the brain.

Ablation of Neuronal Ceramide Synthase 1 in Mice Decreases Ganglioside Levels and Expression of Myelin-associated Glycoprotein in Oligodendrocytes*

An essential function of CerS1-derived ceramide in the regulation of cerebellar development and neurodevelopmentally regulated behavior in mice is revealed.

Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in Npc1 -/- mouse brain.

Results provide strong evidence that cholesterol accumulation-induced changes in autophagy-lysosome function are closely associated with neurodegeneration in NPC.

Lipid Changes in Niemann-Pick Disease Type C Brain: Personal Experience and Review of the Literature

It is indicated that glycolipid changes in brain do not occur before a few months after birth, possibly at a period concomitant with the onset of neurological symptoms, in contrast to the very early glycolIPid abnormalities observed in non-neural organs.

Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann‐Pick type C1‐deficient mouse brains

Age‐related alterations in the level/distribution of APP and its processing enzymes, β‐ and γ‐secretases, in the hippocampus and cerebellum of Npc1−/− mice, a well‐established model of NPC pathology are evaluated to suggest that increased level and processing of APP may be associated with the development of pathology and/or degenerative events observed in Npc2‐/− mouse brains.