The sphingosine 1 ‐phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus

FTY720 is a synthetic analogue of sphingosine 1-phosphate. It is currently used to treat multiple sclerosis and has recently been approved for use in adolescents. The aim of this study was to investigate how FTY720 alters the lipid composition of the brain of adolescent mice. Three weeks of chronic FTY720 treatment caused an up-regulation of 99 lipid species in the mouse hippocampus, including several oxidised phosphatidylcholines, whereas only 3 lipid species of the phosphatidic acid class were down-regulated. Our study presents novel insight into FTY720's molecular mechanism of action in the central nervous system. FST, forced swim test; LC-MS/MS, liquid chromatography –tandem mass spectrometry; MUFAs, monounsaturated fatty acids; MWM, Morris water maze; OFT, open field test; PCOH, hydroxy-phosphatidylcholine; PND, postnatal day; PUFAs, polyunsaturated fatty acids; S1P, sphingosine 1-phosphate; S1PR, sphingosine 1-phosphate receptor. AbstractThe small-molecule drug, FTY720 (fingolimod), is a synthetic sphingosine 1-phosphate (S1P) analogue currently used to treat relapsing –remitting multiple sclerosis in both adults and children. FTY720 can cross the blood–brain barrier (BBB) and, over time, accumulate in lipid-rich areas of the central nervous system (CNS) by incorporating into phospholipid membranes. FTY720 has been shown to enhance cell membrane fluidity, whic h can modulate the functions of glial cells and neuronal populations involved in regulating behaviour. Mo...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research