LAUSR

Omega-3 fatty acids (3-FAs) modulate inflammation and brain-controlled febrile responses during inflammation. Here, we aimed to characterize the distribution and relative concentrations of several lipids (e.g. phosphatidylcholine, PC) including 3-FA-carrying lipids in a brain structure important for immune-to- brain communication, namely the vascular organ of the lamina terminalis (OVLT), during systemic lipopolysaccharide (LPS)-induced inflammation. For this purpose, wild type and fat-1 transgenic mice which produce large quantities of omega 3-FA endogenously, were stimulated with LPS (i.p., 2.5 mg/kg) or saline. Animals were sacrificed (5 h, 24 h), brains and blood samples were collected and analyzed by immunohistochemistry, high-resolution atmospheric-pressure scanning microprobe matrix assisted laser desorption/ionization ion source combined with an orbital trapping mass spectrometer and bioassays, respectively. Telemetric recordings revealed moderate hypothermia in LPS-treated fat-1 mice but fever in wildtype counterparts. Moreover, depending on genotypes and treatment, several distinct distribution patterns were observed for putative inflammation-involved phospholipids [e.g. PC(38:6), LysoPC(16:0)/(18:0), PE (P-36:4)] ranging from equal distributions, accumulation or absence within the OVLT compared to adjacent brain tissue. A localized increase of LysoPCs was indicative of enhanced LPS-induced turnover of fatty acid metabolism in the OVLT in fat-1 mice compared to wild type controls. Overall, screening of lipid distribution patterns revealed distinct inflammation-induced changes in the OVLT highlighting its prominent role for lipid metabolism and brain inflammation. New candidates for brain inflammation and immune-to-brain communication have been detected.