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Endotoxemia rocks sphingolipid metabolism at the blood–brain barrier
Author(s) -
Camerer Eric
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14246
Subject(s) - sphingosine 1 phosphate receptor , sphingolipid , blood–brain barrier , sphingosine 1 phosphate , context (archaeology) , sphingosine , receptor , medicine , biology , endocrinology , pathogenesis , pharmacology , microbiology and biotechnology , chemistry , biochemistry , central nervous system , paleontology
In this issue of the Journal of Neurochemistry , Vutukuri et al . evaluate the impact of endotoxemia‐induced encephalopathy on the sphingosine‐1‐phosphate (S1P) signaling pathway at the blood–brain barrier (BBB). Four hours after intraperitoneal administration of lipopolysaccharides (LPS, 4 mg/kg) to mice, they first demonstrate BBB dysfunction and then evaluate changes in sphingolipid metabolites in serum, isolated brain microvessels (MBMV), and whole brain. In parallel, they investigate the fate of indicated S1P generating and metabolizing enzymes and S1P receptors in brain and MBMV. S1P levels decreased in serum and brain and a similar tendency was observed in MBMV. Sphk2 expression was strongly reduced in MBMV together with an up‐regulation of lipid phosphate and S1P phosphatases, resulting in a net decrease in S1P levels despite a compensatory increase in Sphk1 expression. The implications of disturbed sphingolipid metabolism for the pathogenesis of septic encephalopathy will depend on the net impact of these changes on S1P receptor signaling at the BBB and the importance of the S1P pathway in regulating vascular homeostasis in this context.