Spatially resolved mass spectrometry analysis of amyloid plaque‐associated lipids

Blank, Martina; Hopf, Carsten

doi:10.1111/jnc.15216

Cited by 15 publications

(14 citation statements)

References 99 publications

(174 reference statements)

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“…It has been demonstrated the involvement of LysoPCs, PCs, Ceramides and Sphingomyelins in microglial inflammatory responses [51][52][53] . Particularly in AD, characteristic lipids, such as LysoPC(16:0), LysoPC(18:0), LysoPC(18:1) and Ceramides, were found associated with beta-amyloid plaques 54 . In like manner, these LysoPCs were also found up-regulated in a PD mouse model brain 55 .…”

Section: Discussionmentioning

confidence: 99%

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

Blank

Enzlein

Hopf

2022

Sci Rep

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Pathological microglia activation can promote neuroinflammation in many neurodegenerative diseases, and it has therefore emerged as a potential therapeutic target. Increasing evidence suggests alterations in lipid metabolism as modulators and indicators in microglia activation and its effector functions. Yet, how lipid dynamics in activated microglia is affected by inflammatory stimuli demands additional investigation to allow development of more effective therapies. Here, we report an extensive matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) whole cell fingerprinting workflow to investigate inflammation-associated lipid patterns in SIM-A9 microglial cells. By combining a platform of three synergistic MALDI MS technologies we could detect substantial differences in lipid profiles of lipopolysaccharide (LPS)- stimulated and unstimulated microglia-like cells leading to the identification of 21 potential inflammation-associated lipid markers. LPS-induced lipids in SIM-A9 microglial cells include phosphatidylcholines, lysophosphatidylcholines (LysoPC), sphingolipids, diacylglycerols and triacylglycerols. Moreover, MALDI MS-based cell lipid fingerprinting of LPS-stimulated SIM-A9 microglial cells pre-treated with the non-selective histone deacetylase inhibitor suberoylanilide hydroxamic acid revealed specific modulation of LPS-induced-glycerolipids and LysoPC(18:0) with a significant reduction of microglial inflammation response. Our study introduces MALDI MS as a complementary technology for fast and label-free investigation of stimulus-dependent changes in lipid patterns and their modulation by pharmaceutical agents.

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Section: Discussionmentioning

confidence: 99%

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

Blank

Enzlein

Hopf

2022

Sci Rep

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“…A detailed review of the lipid content of these plaques, as identified through lipidomics studies, has recently been presented ( 58 ). In mouse models, relative to normal tissue, there is an accumulation of fatty acids, cholesterol, sulfatides, and phosphatidylethanolamine lipids in plaques, and a depletion of phosphatidylcholine (PC) lipids.…”

Section: Evidence For the Presence Of Lipids In Amyloid Fibrilsmentioning

confidence: 99%

The association of lipids with amyloid fibrils

Sanderson

2022

Journal of Biological Chemistry

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“…Mass spectrometry is an important tool for probing biomolecular information in heterogeneous biological tissue. Localization, identification, and quantification of biomolecules in tissue sections by mass spectrometry can be achieved with imaging − or by collection and off-line analysis of material from localized regions of interest (ROI). − Mass spectrometry imaging excels at direct determination of the distribution of biomolecules within tissue sections with spatial resolution at micrometer scales. Mass spectrometry imaging (MSI) is rapid in part because it does not include a chromatographic separation step, but for this reason, quantification and identification are challenging.…”

Section: Introductionmentioning

confidence: 99%

Infrared Laser Ablation Microsampling with a Reflective Objective

Dong

Richardson

Solouki

et al. 2022

J. Am. Soc. Mass Spectrom.

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A Schwarzschild reflective objective with a numerical aperture of 0.3 and working distance of 10 cm was used for laser ablation sampling of tissue for off-line mass spectrometry. The objective focused the laser to a diameter of 5 μm and produced 10 μm ablation spots on thin ink films and tissue sections. Rat brain tissue sections 50 μm thick were ablated in transmission geometry, and the ablated material was captured in a microcentrifuge tube containing solvent. Proteins from ablated tissue sections were quantified with a Bradford assay, which indicated that approximately 300 ng of protein was captured from a 1 mm 2 area of ablated tissue. Areas of tissue ranging from 0.01 to 1 mm 2 were ablated and captured for bottom-up proteomics. Proteins were extracted from the captured tissue and digested for liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis for peptide and protein identification.

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Spatially resolved mass spectrometry analysis of amyloid plaque‐associated lipids

Cited by 15 publications

References 99 publications

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

The association of lipids with amyloid fibrils

Infrared Laser Ablation Microsampling with a Reflective Objective

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