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

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
ACS Chem. Neurosci.. 2019-09-12; 10(10): 4394-4406
DOI: 10.1021/acschemneuro.9b00435

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Bredehöft J(1), Bhandari DR(2), Pflieger FJ(1), Schulz S(2), Kang JX(3), Layé S(4), Roth J(1)(5), Gerstberger R(1), Mayer K(6), Spengler B(2), Rummel C(1)(5).

Author information:
(1)Institute of Veterinary Physiology and Biochemistry , Justus Liebig University Giessen , Frankfurter Strasse 100 , D-35392 Giessen , Germany.
(2)Institute of Inorganic and Analytical Chemistry , Justus Liebig University Giessen , Heinrich-Buff-Ring 17 , D-35392 Giessen , Germany.
(3)Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School , 149 13th Street ,
Charlestown , Massachusetts 02129 , United States.
(4)UMR 1286, NutriNeuro: Laboratoire Nutrition et Neurobiologie Intégrée, Institut National de la Recherche Agronomique, Université de Bordeaux, Bordeaux 33076 , France.
(5)Center for Mind, Brain and Behavior (CMBB) , University of Marburg and Justus Liebig University Giessen , Marburg 35032 , Germany.
(6)University of Giessen and Marburg Lung Center (UGMLC) , Justus Liebig University Giessen , Klinikstrasse 33 , Giessen D-35392 , Germany.

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.

DOI: 10.1021/acschemneuro.9b00435
PMID: 31513369

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