Dataset Information

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

ABSTRACT: Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. To complement the imaging studies, a data-processing pipeline was developed to generate consensus mass spectra, thereby using both technical and biological image replicates to assess differences. The consensus spectra are used to determine true differences in lipid relative abundance; lipid distributions can be determined in an unbiased fashion without prior knowledge of location. We show the cerebellar distribution of gangliosides GM1, GM2, and GM3, including variants of lipid chain length. We also performed MALDI-MSI of cholesterol. Further analysis of lobules IV/V and X of the cerebellum gangliosides indicates regional differences. The specificity achieved highlights the power of MSI, and this new workflow demonstrates a universal approach for addressing reproducibility in imaging experiments applied to NPC1.

SUBMITTER: Tobias F

PROVIDER: S-EPMC6277165 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Tobias Fernando F Olson Matthew T MT Cologna Stephanie M SM

Journal of lipid research 20180928 12

Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. To complement the ...[more]

PMID: 30266834

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Project description:OBJECTIVES:The aim of this study was to comprehensively evaluate the auditory phenotype in Niemann-Pick disease, type C1 (NPC1), to understand better the natural history of this complex, heterogeneous disorder, and to define further the baseline auditory deficits associated with NPC1 so that use of potentially ototoxic interventions (e.g., 2-hydroxypropyl-ß-cyclodextrin) may be more appropriately monitored and understood. DESIGN:Fifty patients with NPC1 ranging in age from 4 months to 21 years (mean = 9.3 years) enrolled in a natural history/observational study at the National Institutes of Health. The auditory test battery included, when possible, immittance audiometry, pure-tone and speech audiometry, otoacoustic emission testing, and a neurotologic auditory brainstem response study. Longitudinal data were collected on a subset of patients. RESULTS:Over half of the cohort exhibited hearing loss involving the high frequencies ranging from a slight to moderate degree, and 74% of patients presented with clinically significant hearing loss involving the frequencies most important to speech understanding (0.5, 1, 2, 4 kHz). Despite the heterogeneity of the sample, results among patients were sufficiently consistent to implicate retrocochlear dysfunction in the majority (66%) of individuals, with (22%) or without (44%) accompanying cochlear involvement. Some patients (10%) presented with a profile for auditory neuropathy spectrum disorder. The combination of cross-sectional and longitudinal data indicates these patients are at risk for a progressive decline in auditory function. CONCLUSIONS:This is the largest cohort of patients with NPC1 evaluated comprehensively for auditory dysfunction, and results implicate the pathological processes of NPC1 in the manifestation of hearing loss. Patients with NPC1 should be monitored audiologically throughout their lives, beginning at the time of diagnosis. Clinicians and researchers should be aware of this historically overlooked aspect of the phenotype.

Dataset Information

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

Publications

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

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