Visualizing and Profiling Lipids in the OVLT of Fat-1 and Wild Type Mouse Brains during LPS-Induced Systemic Inflammation Using AP-SMALDI MSI.

Abstract

Lipids, including omega-3 polyunsaturated fatty acids (n-3-PUFAs), modulate brain-intrinsic inflammation during systemic inflammation. The vascular organ of the lamina terminalis (OVLT) is a brain structure important for immune-to-brain communication. We, therefore, aimed to profile the distribution of several lipids (e.g., phosphatidyl-choline/ethanolamine, PC/PE), including n-3-PUFA-carrying lipids (esterified in phospholipids), in the OVLT during systemic lipopolysaccharide(LPS)-induced inflammation. We injected wild type and endogenously n-3-PUFA producing fat-1 transgenic mice with LPS (i.p., 2.5 mg/kg) or PBS. Brain samples were analyzed using immunohistochemistry and high-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization orbital trapping mass spectrometry imaging (AP-SMALDI-MSI) for spatial resolution of lipids. Depending on genotype and treatment, several distinct distribution patterns were observed for lipids [e.g., lyso(L)PC (16:0)/(18:0)] proposed to be involved in inflammation. The distribution patterns ranged from being homogeneously disseminated [LPC (18:1)], absent/reduced signaling within the OVLT relative to adjacent preoptic tissue [PE (38:6)], either treatment- and genotype-dependent or independent low signal intensities [LPC (18:0)], treatment- and genotype-dependent [PC 38:6)] or independent accumulation in the OVLT [PC (38:7)], and accumulation in commissures, e.g., nerve fibers like the optic nerve [LPE (18:1)]. Overall, screening of lipid distribution patterns revealed distinct inflammation-induced changes in the OVLT, highlighting the prominent role of lipid metabolism in brain inflammation. Moreover, known and novel candidates for brain inflammation and immune-to-brain communication were detected specifically within this pivotal brain structure, a window between the periphery and the brain. The biological significance of these newly identified lipids abundant in the OVLT and the adjacent preoptic area remains to be further analyzed.

• Authors: Janne Bredehöft, Dhaka Ram Bhandari, Fabian Johannes Pflieger, Sabine Schulz, Jing X Kang, Sophie Layé, Joachim Roth, Rüdiger Gerstberger, Konstantin Mayer, Bernhard Spengler, Christoph Rummel
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 10 Issue 10 Pg. 4394-4406 (10 16 2019) ISSN: 1948-7193 [Electronic] United States
• PMID: 31513369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Lipids
• Lipopolysaccharides
• fat1 protein, mouse

Topics

• Animals
• Cadherins (genetics, metabolism)
• Inflammation (chemically induced, metabolism)
• Lipid Metabolism
• Lipids (analysis)
• Lipopolysaccharides
• Male
• Mice
• Mice, Transgenic
• Organum Vasculosum (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization