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

Martina Blank1,2, Thomas Enzlein3, Carsten Hopf4,5

  • 1Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack Str. 10, 68163, Mannheim, Germany. martina.blank@ufsc.br.

Scientific Reports
|February 22, 2022
PubMed

Insights

Matrix-assisted laser desorption/ionization mass spectrometry identified 21 lipid markers associated with microglial inflammation. This technique also revealed how suberoylanilide hydroxamic acid reduces neuroinflammation by modulating lipid profiles in microglia.

Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • Pathological microglia activation drives neuroinflammation in neurodegenerative diseases, making it a therapeutic target.
  • Altered lipid metabolism is increasingly recognized as a key factor in microglia activation and function.
  • Understanding lipid dynamics in activated microglia is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate inflammation-associated lipid patterns in microglia using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS).
  • To identify potential lipid markers of microglial activation and inflammation.
  • To explore the modulatory effects of pharmaceutical agents on microglial lipid profiles and inflammatory responses.

Main Methods:

  • Developed and applied an extensive MALDI MS whole-cell fingerprinting workflow for SIM-A9 microglial cells.
  • Utilized a synergistic platform of three MALDI MS technologies for comprehensive lipid profiling.
  • Investigated lipid profile changes in response to lipopolysaccharide (LPS) stimulation and suberoylanilide hydroxamic acid treatment.

Main Results:

  • Identified 21 potential inflammation-associated lipid markers, including phosphatidylcholines, lysophosphatidylcholines (LysoPC), sphingolipids, diacylglycerols, and triacylglycerols.
  • Observed substantial differences in lipid profiles between LPS-stimulated and unstimulated microglia.
  • Demonstrated that suberoylanilide hydroxamic acid specifically modulates LPS-induced glycerolipids and LysoPC(18:0), significantly reducing microglial inflammation.

Conclusions:

  • MALDI MS is a valuable, label-free technology for rapid investigation of stimulus-dependent lipid changes in microglia.
  • This approach facilitates the identification of novel lipid biomarkers for neuroinflammation.
  • MALDI MS-based lipid fingerprinting can assess the efficacy of pharmaceutical agents in modulating microglial inflammatory responses.

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