参考文献:1. Allende ML, Bektas M, Lee BG, Bonifacino E, Kang J, Tuymetova G, Chen W, Saba JD, Proia RL (2011) Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil trafficking. J Biol Chem 286:7348-358 CrossRef 2. Alvarez SE, Harikumar KB, Hait NC, Allegood J, Strub GM, Kim EY, Maceyka M, Jiang H, Luo C, Kordula T (2010) Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature 465:1084-088 CrossRef 3. Araujo D, Lapchak P, Robitaille Y, Gauthier S, Quirion R (1988) Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer’s disease. J Neurochem 50:1914-923 CrossRef 4. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 277:21453-1457 CrossRef 5. Chalfant CE, Spiegel S (2005) Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J Cell Sci 118:4605-612 CrossRef 6. Ching LK, Mompoint F, Guderian JA, Picone A, Orme IM, Coler RN, Reed SG, Baldwin SL (2011) Transcriptional profiling of TLR-4/7/8-stimulated guinea pig splenocytes and whole blood by bDNA assay. J Immunol Methods 373:54-2 CrossRef 7. Cohen JA, Barkhof F, Comi G, Hartung H-P, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. New Engl J Med 362:402-15 CrossRef 8. Corbyn Z (2013) New set of Alzheimer’s trials focus on prevention. Lancet 381:614-15 CrossRef 9. Cyster JG (2005) Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu Rev Immunol 23:127-59 CrossRef 10. Cyster JG (2010) B cell follicles and antigen encounters of the third kind. Nat Immunol 11:989-96 CrossRef 11. Czech B, Pfeilschifter W, Mazaheri-Omrani N, Strobel MA, Kahles T, Neumann-Haefelin T, Rami A, Huwiler A, Pfeilschifter J (2009) The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia. Biochem Biophys Res Commun 389:251-56 CrossRef 12. Deogracias R, Yazdani M, Dekkers MP, Guy J, Ionescu MCS, Vogt KE, Barde Y-A (2012) Fingolimod, a sphingosine-1 phosphate receptor modulator increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc Natl Acad Sci USA 109:14230-4235 CrossRef 13. Donahue DA, Dougherty EJ, Meserve LA (2004) Influence of a combination of two tetrachlorobiphenyl congeners (PCB 47; PCB 77) on thyroid status, choline acetyltransferase (ChAT) activity, and short-and long-term memory in 30-day-old Sprague–Dawley rats. Toxicology 203:99-07 CrossRef 14. Eklind S, Hagberg H, Wang X, S?vman K, Leverin A-L, Hedtj?rn M, Mallard C (2006) Effect of lipopolysaccharide on global gene expression in the immature rat brain. Pediatr Res 60:161-68 CrossRef 15. El Alwani M, Wu BX, Obeid LM, Hannun YA (2006) Bioactive sphingolipids in the modulation of the inflammatory response. Pharmacol Ther 112:171-83 Behzad Khallaghi (2) Zahurin Mohamed (1) Murali Naidu (4) Abolhassan Ahmadiani (1) (2) Leila Dargahi (5)
Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal’s brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.