Dataset Information

Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.

ABSTRACT: Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and during brain development. MSI revealed that in the adult mouse, cholesterol is the highest in the pons and medulla and how its distribution changes during development. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience.

SUBMITTER: Angelini R

PROVIDER: S-EPMC7992047 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.

Angelini Roberto R Yutuc Eylan E Wyatt Mark F MF Newton Jillian J Yusuf Fowzi A FA Griffiths Lauren L Cooze Benjamin J BJ El Assad Dana D Frache Gilles G Rao Wei W Allen Luke B LB Korade Zeljka Z Nguyen Thu T A TTA Rathnayake Rathnayake A C RAC Cologna Stephanie M SM Howell Owain W OW Clench Malcolm R MR Wang Yuqin Y Griffiths William J WJ

Analytical chemistry 20210309 11

Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and duri ...[more]

PMID: 33687199

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Project description:Quantitative mass spectrometry imaging (MSI) is an effective technique for determining the spatial distribution of molecules in a variety of sample types; however, the quality of the ion signals is related to the chemical and morphological properties of the tissue and the targeted analyte(s). Issues may arise with the incorporation of standards into the tissue at repeatable, well-defined concentrations, as well as with the extraction and incorporation of endogenous analytes versus standards from tissue into the matrix. To address these concerns, we combine imprint MSI (iMSI) with kinetic calibration and use it to quantify lipids in rat brain tissue samples. Briefly, tissues were imprinted on slides coated with a dopamine-modified TiO2 monolith pretreated with analyte standards, resulting in the adsorption of endogenous analytes onto the coating and desorption of standards into the tissue. The incorporation of standards into the tissue enabled quantification of the measured analytes using kinetic calibration. Moreover, matrix effects were reduced, and the intensities of analyte standard signals became more uniform. The symmetry of the adsorption of endogenous ceramides and the desorption of ceramide standards suggest that the content of adsorbed endogenous ceramide can be determined by measuring the content of desorbed ceramide standard. Using kinetic calibration, endogenous ceramide concentrations were calculated for a range of dry and wet tissue imprinting conditions and compared to quantitative MSI using a standard spiking approach. We validated the relative quantitative values from iMSI using liquid chromatography tandem mass spectrometry (LC-MS/MS) and found that the ratios from iMSI as compared to LC-MS/MS were in the range of 70-200% over the concentration range of endogenous ceramides; the correlation coefficient between iMSI and LC-MS/MS was over 0.9 (Pearson's r), while the relative recoveries via traditional standard spiking were between 200% and 5000% depending on the brain region and sample preparation conditions.

Dataset Information

Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.

Publications

Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.

Similar Datasets

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