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

Int J Mol Sci. 2024 Nov 8;25(22):12032. doi: 10.3390/ijms252212032.

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.

Keywords: DESI; MALDI; TOF-SIMS; mass spectrometry imaging; neuroinflammation.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Carnitine / analogs & derivatives
  • Carnitine / metabolism
  • Disease Models, Animal
  • Endocannabinoids / metabolism
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lipid Metabolism / drug effects
  • Lipids
  • Lipopolysaccharides*
  • Male
  • Mass Spectrometry / methods
  • Microglia / drug effects
  • Microglia / metabolism
  • Neuroinflammatory Diseases* / metabolism
  • Phosphatidylethanolamines / metabolism
  • Rats

Substances

  • Lipopolysaccharides
  • Phosphatidylethanolamines
  • Lipids
  • acylcarnitine
  • Carnitine
  • Endocannabinoids

Grants and funding

The UK Engineering and Physical Sciences Research Council (EPSRC) and the Henry Royce Institute funded the TOF-SIMS instrumentation used in this work, including grants EP/S019863/1, EP/R00661X/1, EP/P025021/1 and EP/P025498/1.