Visualizing and Profiling Lipids in the OVLT of Fat-1 and Wild Type Mouse Brains during LPS-Induced Systemic Inflammation Using AP-SMALDI MSI
ACS Chem. Neurosci.. 2019-09-12; 10(10): 4394-4406
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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).
(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.