Accumulation of Bioactive Lipid Species in LPS-Induced Neuroinflammation Models Analysed with Multi-Modal Mass Spectrometry Imaging

Irma Berrueta Razo, Kerry Shea, Tiffany-Jayne Allen, Hervé Boutin, Adam McMahon, Nicholas Lockyer, Philippa J Hart

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroinflammation is a complex biological process related to a variety of pathologies, often requiring better understanding in order to develop new, targeted therapeutic interventions. Within this context, multimodal Mass Spectrometry Imaging (MSI) has been used to characterise molecular changes in neuroinflammation for biomarker discovery not possible to other techniques. In this study, molecules including bioactive lipids were detected across inflamed regions of the brain in rats treated with lipopolysaccharide (LPS). The detected lipids may be acting as inflammatory mediators of the immune response. We identified that N-acyl-phosphatidylethanolamine (NAPE) species accumulated in the inflamed area. The presence of these lipids could be related to the endocannabinoid (eCB) signalling system, mediating an anti-inflammatory response from microglial cells at the site of injury to balance pro-inflammation and support neuronal protection. In addition, polyunsaturated fatty acids (PUFAs), specifically n-3 and n-6 species, were observed to accumulate in the area where LPS was injected. PUFAs are directly linked to anti-inflammatory mediators resolving inflammation. Finally, acylcarnitine species accumulated around the inflammation region. Accumulation of these molecules could be due to a deficient β-oxidation cycle.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume25
Issue number22
DOIs
Publication statusPublished - 8 Nov 2024

Keywords

  • Animals
  • Lipopolysaccharides
  • Rats
  • Neuroinflammatory Diseases/metabolism
  • Male
  • Phosphatidylethanolamines/metabolism
  • Mass Spectrometry/methods
  • Disease Models, Animal
  • Brain/metabolism
  • Lipids
  • Carnitine/metabolism
  • Endocannabinoids/metabolism
  • Inflammation/metabolism
  • Lipid Metabolism/drug effects
  • Microglia/metabolism

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