Skip to main content
SpringerLink
Log in
Book cover

Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases pp 149–170Cite as

Sphingosine-1 Phosphate and Central Nervous System

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 378))

Abstract

The development of fingolimod, an unselective functional antagonist of the interactions between sphingosine 1 phosphate (S1P) and sphingosine 1 phosphate receptors (S1PRs), as the first oral therapy for multiple sclerosis (MS) has been a milestone. The parallel intensive research on the role of S1P, sphingosine kinases, and the five known S1PRs, their tissue distribution and expression in physiological and pathological conditions have led to a wide range of interesting findings. The initial focus of this research in the context of developing fingolimod as a treatment of MS has been on its immunological effects. The wide distribution and important roles of sphingosine, its metabolites, and their receptors in the central nervous system (CNS) in general, in myelin, and in all cell types of this organ have spurred interest to examine S1P and its five receptors in the brain as well. The present review will concentrate on the latter area and give a brief overview of what is known about S1P/S1PR interactions in the CNS in physiological and pathological conditions.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Akahoshi N, Ishizaki Y, Yasuda H, Murashima YL, Shinba T, Goto K, Himi T, Chun J, Ishii I (2011) Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2. Epilepsy Behav 22:659–665

    PubMed  Google Scholar 

  • Ascherio A, Munger K (2008) Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 28:17–28

    PubMed  Google Scholar 

  • Barkhof F, Calabresi PA, Miller DH, Reingold SC (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5:256–266

    PubMed  Google Scholar 

  • Bartholomäus I, Schläger C, Brinkmann V, Wekerle H, Flügel A (2008) Intravital 2-photon imaging of encephalitogenic effector cells during fingolimod (FTY720) treatment of experimental autoimmune encephalomyelitis. World Congress on Treatment and Research in Multiple Sclerosis (ECTRIMS), Montreal. Poster P7

    Google Scholar 

  • Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, Cotsapas C, Shah TS, Spencer C, Booth D, Goris A et al (2013) Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 45:1353–1360

    CAS  PubMed  Google Scholar 

  • Benarroch EE (2013) Microglia: multiple roles in surveillance, circuit shaping, and response to injury. Neurology 81:1079–1088

    PubMed  Google Scholar 

  • Bieberich E (2011) There is more to a lipid than just being a fat: sphingolipid-guided differentiation of oligodendroglial lineage from embryonic stem cells. Neurochem Res 36:1601–1611

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boulton C, Meiser K, David OJ, Schmouder R (2012) Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebo-controlled, parallel-group, multiple-dose study. J Clin Pharmacol 52:1879–1890

    CAS  PubMed  Google Scholar 

  • Brana C, Frossard MJ, Pescini Gobert R, Martinier N, Boschert U, Seabrook TJ (2013) Immunohistochemical detection of sphingosine-1-phosphate receptor 1 and 5 in human multiple sclerosis lesions. Neuropathol Appl Neurobiol

    Google Scholar 

  • Brinkmann V (2007) Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther 115:84–105

    CAS  PubMed  Google Scholar 

  • Brinkmann V (2009) FTY720 (fingolimod) in multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol 158:1173–1182

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brinkmann V, Chen S, Feng L, Pinschewer D, Nikolova Z, Hof R (2001) FTY720 alters lymphocyte homing and protects allografts without inducing general immunosuppression. Transplant Proc 33:530–531

    CAS  PubMed  Google Scholar 

  • Brinkmann V, Cyster JG, Hla T (2004) FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 4:1019–1025

    CAS  PubMed  Google Scholar 

  • Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9:883–897

    CAS  PubMed  Google Scholar 

  • Bryan L, Kordula T, Spiegel S, Milstien S (2008a) Regulation and functions of sphingosine kinases in the brain. Biochim Biophys Acta 1781:459–466

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bryan L, Paugh BS, Kapitonov D, Wilczynska KM, Alvarez SM, Singh SK, Milstien S, Spiegel S, Kordula T (2008b) Sphingosine-1-phosphate and interleukin-1 independently regulate plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor expression in glioblastoma cells: implications for invasiveness. Mol Cancer Res 6:1469–1477

    CAS  PubMed Central  PubMed  Google Scholar 

  • Callihan P, Hooks SB (2012) Sphingosine-1-phosphate signaling in neural progenitors. Methods Mol Biol 874:193–200

    CAS  PubMed  Google Scholar 

  • Callihan P, Zitomer NC, Stoeling MV, Kennedy PC, Lynch KR, Riley RT, Hooks SB (2012) Distinct generation, pharmacology, and distribution of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate in human neural progenitor cells. Neuropharmacology 62:988–996

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cannon RE, Peart JC, Hawkins BT, Campos CR, Miller DS (2012) Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain. Proc Natl Acad Sci USA 109:15930–15935

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chakraborty G, Saito M, Shah R, Mao RF, Vadasz C, Saito M (2012) Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in the developing mouse brain. J Neurochem 121:806–817

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, Noguchi K, Teo ST, Yung YC, Lu M, Kennedy G et al (2011) FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci USA 108:751–756

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chun J, Hartung HP (2010) Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 33:91–101

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coelho RP, Payne SG, Bittman R, Spiegel S, Sato-Bigbee C (2007) The immunomodulator FTY720 has a direct cytoprotective effect in oligodendrocyte progenitors. J Pharmacol Exp Ther 323:626–635

    CAS  PubMed  Google Scholar 

  • Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415

    CAS  PubMed  Google Scholar 

  • Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL et al (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380:1829–1839

    CAS  PubMed  Google Scholar 

  • Contos JJ, Ishii I, Fukushima N, Kingsbury MA, Ye X, Kawamura S, Brown JH, Chun J (2002) Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol Cell Biol 22:6921–6929

    CAS  PubMed Central  PubMed  Google Scholar 

  • Deogracias R, Yazdani M, Dekkers MP, Guy J, Ionescu MC, Vogt KE, Barde YA (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 109:14230–14235

    CAS  PubMed Central  PubMed  Google Scholar 

  • Doi Y, Takeuchi H, Horiuchi H, Hanyu T, Kawanokuchi J, Jin S, Parajuli B, Sonobe Y, Mizuno T, Suzumura A (2013) Fingolimod phosphate attenuates oligomeric amyloid beta-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons. PLoS ONE 8:e61988

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dubin AE, Herr DR, Chun J (2010) Diversity of lysophosphatidic acid receptor-mediated intracellular calcium signaling in early cortical neurogenesis. J Neurosci 30:7300–7309

    CAS  PubMed Central  PubMed  Google Scholar 

  • Durafourt BA, Lambert C, Johnson TA, Blain M, Bar-Or A, Antel JP (2011) Differential responses of human microglia and blood-derived myeloid cells to FTY720. J Neuroimmunol 230:10–16

    CAS  PubMed  Google Scholar 

  • Edsall LC, Pirianov GG, Spiegel S (1997) Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J Neurosci 17:6952–6960

    CAS  PubMed  Google Scholar 

  • Engelhardt B (2011) Neuroscience. Blood-brain barrier differentiation. Science 334:1652–1653

    CAS  PubMed  Google Scholar 

  • Estrada-Bernal A, Palanichamy K, Ray Chaudhury A, van Brocklyn JR (2012) Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma. Neuro Oncol 14:405–415

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fujino M, Funeshima N, Kitazawa Y, Kimura H, Amemiya H, Suzuki S, Li XK (2003) Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J Pharmacol Exp Ther 305:70–77

    CAS  PubMed  Google Scholar 

  • Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI et al (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 367:1098–1107

    CAS  PubMed  Google Scholar 

  • Goldmann T, Prinz M (2013) Role of microglia in CNS autoimmunity. Clin Dev Immunol 2013:208093

    PubMed Central  PubMed  Google Scholar 

  • Grigorova IL, Schwab SR, Phan TG, Pham TH, Okada T, Cyster JG (2009) Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat Immunol 10:58–65

    CAS  PubMed Central  PubMed  Google Scholar 

  • Groves A, Kihara Y, Chun J (2013) Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy. J Neurol Sci 328:9–18

    CAS  PubMed  Google Scholar 

  • Haghikia A, Hohlfeld R, Gold R, Fugger L (2013) Therapies for multiple sclerosis: translational achievements and outstanding needs. Trends Mol Med 19:309–319

    CAS  PubMed  Google Scholar 

  • Hasegawa Y, Suzuki H, Sozen T, Rolland W, Zhang JH (2010) Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke 41:368–374

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hohlfeld R, Barkhof F, Polman C (2011) Future clinical challenges in multiple sclerosis: relevance to sphingosine 1-phosphate receptor modulator therapy. Neurology 76:S28–S37

    CAS  PubMed  Google Scholar 

  • Ishii I, Ye X, Friedman B, Kawamura S, Contos JJ, Kingsbury MA, Yang AH, Zhang G, Brown JH, Chun J (2002) Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3. J Biol Chem 277:25152–25159

    CAS  PubMed  Google Scholar 

  • Jackson SJ, Giovannoni G, Baker D (2011) Fingolimod modulates microglial activation to augment markers of remyelination. J Neuroinflammation 8:76

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jaillard C, Harrison S, Stankoff B, Aigrot MS, Calver AR, Duddy G, Walsh FS, Pangalos MN, Arimura N, Kaibuchi K et al (2005) Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci 25:1459–1469

    CAS  PubMed  Google Scholar 

  • Johnson TA, Evans BL, Durafourt BA, Blain M, Lapierre Y, Bar-Or A, Antel JP (2011) Reduction of the peripheral blood CD56(bright) NK lymphocyte subset in FTY720-treated multiple sclerosis patients. J Immunol 187:570–579

    CAS  PubMed  Google Scholar 

  • Jung CG, Kim HJ, Miron VE, Cook S, Kennedy TE, Foster CA, Antel JP, Soliven B (2007) Functional consequences of S1P receptor modulation in rat oligodendroglial lineage cells. Glia 55:1656–1667

    CAS  PubMed  Google Scholar 

  • Kajimoto T, Okada T, Yu H, Goparaju SK, Jahangeer S, Nakamura S (2007) Involvement of sphingosine-1-phosphate in glutamate secretion in hippocampal neurons. Mol Cell Biol 27:3429–3440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L et al (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362:387–401

    CAS  PubMed  Google Scholar 

  • Kataoka H, Sugahara K, Shimano K, Teshima K, Koyama M, Fukunari A, Chiba K (2005) FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration. Cell Mol Immunol 2:439–448

    CAS  PubMed  Google Scholar 

  • Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A (2007) Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13:1173–1175

    CAS  PubMed  Google Scholar 

  • Kim HJ, Miron VE, Dukala D, Proia RL, Ludwin SK, Traka M, Antel JP, Soliven B (2011) Neurobiological effects of sphingosine 1-phosphate receptor modulation in the cuprizone model. FASEB J 25:1509–1518

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kimura A, Ohmori T, Ohkawa R, Madoiwa S, Mimuro J, Murakami T, Kobayashi E, Hoshino Y, Yatomi Y, Sakata Y (2007) Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 25:115–124

    CAS  PubMed  Google Scholar 

  • Kimura A, Ohmori T, Kashiwakura Y, Ohkawa R, Madoiwa S, Mimuro J, Shimazaki K, Hoshino Y, Yatomi Y, Sakata Y (2008) Antagonism of sphingosine 1-phosphate receptor-2 enhances migration of neural progenitor cells toward an area of brain. Stroke 39:3411–3417

    CAS  PubMed  Google Scholar 

  • Kleinschmidt-DeMasters BK, Miravalle A, Schowinsky J, Corboy J, Vollmer T (2012) Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab. J Neuropathol Exp Neurol 71:604–617

    CAS  PubMed  Google Scholar 

  • Kono M, Belyantseva IA, Skoura A, Frolenkov GI, Starost MF, Dreier JL, Lidington D, Bolz SS, Friedman TB, Hla T et al (2007) Deafness and stria vascularis defects in S1P2 receptor-null mice. J Biol Chem 282:10690–10696

    CAS  PubMed  Google Scholar 

  • Lassmann H (2013) Multiple sclerosis: lessons from molecular neuropathology. Exp Neurol

    Google Scholar 

  • Lee KD, Chow WN, Sato-Bigbee C, Graf MR, Graham RS, Colello RJ, Young HF, Mathern BE (2009) FTY720 reduces inflammation and promotes functional recovery after spinal cord injury. J Neurotrauma 26:2335–2344

    PubMed Central  PubMed  Google Scholar 

  • Lewis ND, Haxhinasto SA, Anderson SM, Stefanopoulos DE, Fogal SE, Adusumalli P, Desai SN, Patnaude LA, Lukas SM, Ryan KR et al (2013) Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3. J Immunol 190:3533–3540

    CAS  PubMed  Google Scholar 

  • Leypoldt F, Munchau A, Moeller F, Bester M, Gerloff C, Heesen C (2009) Hemorrhaging focal encephalitis under fingolimod (FTY720) treatment: a case report. Neurology 72:1022–1024

    CAS  PubMed  Google Scholar 

  • Lovett-Racke AE, Yang Y, Racke MK (2011) Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis? Biochim Biophys Acta 1812:246–251

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717

    CAS  PubMed  Google Scholar 

  • MacLennan AJ, Carney PR, Zhu WJ, Chaves AH, Garcia J, Grimes JR, Anderson KJ, Roper SN, Lee N (2001) An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. Eur J Neurosci 14:203–209

    CAS  PubMed  Google Scholar 

  • Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355–360

    CAS  PubMed  Google Scholar 

  • Mehling M, Brinkmann V, Antel J, Bar-Or A, Goebels N, Vedrine C, Kristofic C, Kuhle J, Lindberg RL, Kappos L (2008) FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology 71:1261–1267

    CAS  PubMed  Google Scholar 

  • Mehling M, Johnson TA, Antel J, Kappos L, Bar-Or A (2011) Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 76:S20–S27

    CAS  PubMed  Google Scholar 

  • Meno-Tetang GM, Li H, Mis S, Pyszczynski N, Heining P, Lowe P, Jusko WJ (2006) Physiologically based pharmacokinetic modeling of FTY720 (2-amino-2[2-(-4-octylphenyl)ethyl]propane-1,3-diol hydrochloride) in rats after oral and intravenous doses. Drug Metab Dispos 34:1480–1487

    CAS  PubMed  Google Scholar 

  • Metzler B, Gfeller P, Wieczorek G, Li J, Nuesslein-Hildesheim B, Katopodis A, Mueller M, Brinkmann V (2008) Modulation of T cell homeostasis and alloreactivity under continuous FTY720 exposure. Int Immunol 20:633–644

    CAS  PubMed  Google Scholar 

  • Michaud J, Im DS, Hla T (2010) Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during inflammation. J Immunol 184:1475–1483

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miron VE, Schubart A, Antel JP (2008a) Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci 274:13–17

    CAS  PubMed  Google Scholar 

  • Miron VE, Hall JA, Kennedy TE, Soliven B, Antel JP (2008b) Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod. Am J Pathol 173:1143–1152

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miron VE, Ludwin SK, Darlington PJ, Jarjour AA, Soliven B, Kennedy TE, Antel JP (2010) Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slices. Am J Pathol 176:2682–2694

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miron VE, Durafourt BA, Antel JP, Kennedy TE (2012) Assessment of sphingosine-1-phosphate receptor expression and associated intracellular signaling cascades in primary cells of the human central nervous system. Methods Mol Biol 874:141–154

    CAS  PubMed  Google Scholar 

  • Mizugishi K, Yamashita T, Olivera A, Miller GF, Spiegel S, Proia RL (2005) Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 25:11113–11121

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mok SW, Proia RL, Brinkmann V, Mabbott NA (2012) B cell-specific S1PR1 deficiency blocks prion dissemination between secondary lymphoid organs. J Immunol 188:5032–5040

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mullershausen F, Craveiro LM, Shin Y, Cortes-Cros M, Bassilana F, Osinde M, Wishart WL, Guerini D, Thallmair M, Schwab ME et al (2007) Phosphorylated FTY720 promotes astrocyte migration through sphingosine-1-phosphate receptors. J Neurochem 102:1151–1161

    CAS  PubMed  Google Scholar 

  • Nishimura H, Akiyama T, Irei I, Hamazaki S, Sadahira Y (2010) Cellular localization of sphingosine-1-phosphate receptor 1 expression in the human central nervous system. J Histochem Cytochem 58:847–856

    CAS  PubMed Central  PubMed  Google Scholar 

  • Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343:938–952

    CAS  PubMed  Google Scholar 

  • Novgorodov AS, El-Alwani M, Bielawski J, Obeid LM, Gudz TI (2007) Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration. FASEB J 21:1503–1514

    CAS  PubMed  Google Scholar 

  • O’Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A et al (2011) Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 365:1293–1303

    PubMed  Google Scholar 

  • Oo ML, Thangada S, Wu MT, Liu CH, Macdonald TL, Lynch KR, Lin CY, Hla T (2007) Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor. J Biol Chem 282:9082–9089

    CAS  PubMed  Google Scholar 

  • Oo ML, Chang SH, Thangada S, Wu MT, Rezaul K, Blaho V, Hwang SI, Han DK, Hla T (2011) Engagement of S1P(1)-degradative mechanisms leads to vascular leak in mice. J Clin Invest 121:2290–2300

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG et al (2007) Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316:295–298

    CAS  PubMed  Google Scholar 

  • Peters A, Lee Y, Kuchroo VK (2011) The many faces of Th17 cells. Curr Opin Immunol 23:702–706

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pinschewer DD, Ochsenbein AF, Odermatt B, Brinkmann V, Hengartner H, Zinkernagel RM (2000) FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J Immunol 164:5761–5770

    CAS  PubMed  Google Scholar 

  • Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A et al (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910

    CAS  PubMed  Google Scholar 

  • Rao TS, Lariosa-Willingham KD, Lin FF, Palfreyman EL, Yu N, Chun J, Webb M (2003) Pharmacological characterization of lysophospholipid receptor signal transduction pathways in rat cerebrocortical astrocytes. Brain Res 990:182–194

    CAS  PubMed  Google Scholar 

  • Rau CR, Hein K, Sattler MB, Kretzschmar B, Hillgruber C, McRae BL, Diem R, Bahr M (2011) Anti-inflammatory effects of FTY720 do not prevent neuronal cell loss in a rat model of optic neuritis. Am J Pathol 178:1770–1781

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ricklin ME, Lorscheider J, Waschbisch A, Paroz C, Mehta SK, Pierson DL, Kuhle J, Fischer-Barnicol B, Sprenger T, Lindberg RL et al (2013) T-cell response against varicella-zoster virus in fingolimod-treated MS patients. Neurology 81:174–181

    CAS  PubMed  Google Scholar 

  • Rosado FG, Kim AS (2013) Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol 139:713–727

    CAS  PubMed  Google Scholar 

  • Rossi S, Lo Giudice T, De Chiara V, Musella A, Studer V, Motta C, Bernardi G, Martino G, Furlan R, Martorana A et al (2012) Oral fingolimod rescues the functional deficits of synapses in experimental autoimmune encephalomyelitis. Br J Pharmacol 165:861–869

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sallusto F, Zielinski CE, Lanzavecchia A (2012) Human Th17 subsets. Eur J Immunol 42:2215–2220

    CAS  PubMed  Google Scholar 

  • Sim-Selley LJ, Goforth PB, Mba MU, Macdonald TL, Lynch KR, Milstien S, Spiegel S, Satin LS, Welch SP, Selley DE (2009) Sphingosine-1-phosphate receptors mediate neuromodulatory functions in the CNS. J Neurochem 110:1191–1202

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sinha RK, Park C, Hwang IY, Davis MD, Kehrl JH (2009) B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis. Immunity 30:434–446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sorensen SD, Nicole O, Peavy RD, Montoya LM, Lee CJ, Murphy TJ, Traynelis SF, Hepler JR (2003) Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol Pharmacol 64:1199–1209

    CAS  PubMed  Google Scholar 

  • Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747

    CAS  PubMed  Google Scholar 

  • Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397–407

    CAS  PubMed  Google Scholar 

  • Stone LA, Smith ME, Albert PS, Bash CN, Maloni H, Frank JA, McFarland HF (1995) Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. Neurology 45:1122–1126

    CAS  PubMed  Google Scholar 

  • Takasugi N, Sasaki T, Ebinuma I, Osawa S, Isshiki H, Takeo K, Tomita T, Iwatsubo T (2013) FTY720/fingolimod, a sphingosine analogue, reduces amyloid-beta production in neurons. PLoS ONE 8:e64050

    CAS  PubMed Central  PubMed  Google Scholar 

  • Terai K, Soga T, Takahashi M, Kamohara M, Ohno K, Yatsugi S, Okada M, Yamaguchi T (2003) Edg-8 receptors are preferentially expressed in oligodendrocyte lineage cells of the rat CNS. Neuroscience 116:1053–1062

    CAS  PubMed  Google Scholar 

  • Toman RE, Payne SG, Watterson KR, Maceyka M, Lee NH, Milstien S, Bigbee JW, Spiegel S (2004) Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. J Cell Biol 166:381–392

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vajkoczy P, Laschinger M, Engelhardt B (2001) Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J Clin Invest 108:557–565

    CAS  PubMed Central  PubMed  Google Scholar 

  • van Doorn R, van Horssen J, Verzijl D, Witte M, Ronken E, van Het Hof B, Lakeman K, Dijkstra CD, van Der Valk P, Reijerkerk A et al (2010) Sphingosine 1-phosphate receptor 1 and 3 are upregulated in multiple sclerosis lesions. Glia 58:1465–1476

    PubMed  Google Scholar 

  • van Doorn R, Nijland PG, Dekker N, Witte ME, Lopes-Pinheiro MA, van het Hof B, Kooij G, Reijerkerk A, Dijkstra C, van van der Valk P et al (2012a) Fingolimod attenuates ceramide-induced blood-brain barrier dysfunction in multiple sclerosis by targeting reactive astrocytes. Acta Neuropathol 124:397–410

    CAS  PubMed  Google Scholar 

  • van Doorn R, Lopes Pinheiro MA, Kooij G, Lakeman K, van het Hof B, van der Pol SM, Geerts D, van Horssen J, van der Valk P, van der Kam E et al (2012b) Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier. J Neuroinflammation 9:133

    PubMed Central  PubMed  Google Scholar 

  • Wacker BK, Perfater JL, Gidday JM (2012) Hypoxic preconditioning induces stroke tolerance in mice via a cascading HIF, sphingosine kinase, and CCL2 signaling pathway. J Neurochem 123:954–962

    CAS  PubMed Central  PubMed  Google Scholar 

  • Waubant E, Goodkin DE, Gee L, Bacchetti P, Sloan R, Stewart T, Andersson PB, Stabler G, Miller K (1999) Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology 53:1397–1401

    CAS  PubMed  Google Scholar 

  • Webb M, Tham CS, Lin FF, Lariosa-Willingham K, Yu N, Hale J, Mandala S, Chun J, Rao TS (2004) Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol 153:108–121

    CAS  PubMed  Google Scholar 

  • Wei Y, Yemisci M, Kim HH, Yung LM, Shin HK, Hwang SK, Guo S, Qin T, Alsharif N, Brinkmann V et al (2011) Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol 69:119–129

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu YP, Mizugishi K, Bektas M, Sandhoff R, Proia RL (2008) Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease. Hum Mol Genet 17:2257–2264

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu C, Leong SY, Moore CS, Cui QL, Gris P, Bernier LP, Johnson TA, Seguela P, Kennedy TE, Bar-Or A et al (2013) Dual effects of daily FTY720 on human astrocytes in vitro: relevance for neuroinflammation. J Neuroinflammation 10:41

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang J, Noyan-Ashraf MH, Meissner A, Voigtlaender-Bolz J, Kroetsch JT, Foltz W, Jaffray D, Kapoor A, Momen A, Heximer SP et al (2012) Proximal cerebral arteries develop myogenic responsiveness in heart failure via tumor necrosis factor-alpha-dependent activation of sphingosine-1-phosphate signaling. Circulation 126:196–206

    CAS  PubMed  Google Scholar 

  • Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356:63–66

    CAS  PubMed  Google Scholar 

  • Young N, Pearl DK, van Brocklyn JR (2009) Sphingosine-1-phosphate regulates glioblastoma cell invasiveness through the urokinase plasminogen activator system and CCN1/Cyr61. Mol Cancer Res 7:23–32

    CAS  PubMed Central  PubMed  Google Scholar 

  • Young KL, Brandt AU, Petzold A, Reitz LY, Lintze F, Paul F, Martin R, Schippling S (2013) Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis. Eur J Neurol 20:803–811

    CAS  PubMed  Google Scholar 

  • Yu N, Lariosa-Willingham KD, Lin FF, Webb M, Rao TS (2004) Characterization of lysophosphatidic acid and sphingosine-1-phosphate-mediated signal transduction in rat cortical oligodendrocytes. Glia 45:17–27

    PubMed  Google Scholar 

  • Zhu D, Wang Y, Singh I, Bell RD, Deane R, Zhong Z, Sagare A, Winkler EA, Zlokovic BV (2010) Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. Blood 115:4963–4972

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

R. Martin, M. Sospedra and the Neuroimmunology and MS Resarch Section are supported by the Clinical Research Priority Program MS of the University Zurich.

Author information

Authors and Affiliations

  1. Neuroimmunology and Multiple Sclerosis Research, Clinic for Neurology, University Hospital Zurich, University Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland

    Roland Martin & Mireia Sospedra

Authors
  1. Roland Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mireia Sospedra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roland Martin .

Editor information

Editors and Affiliations

  1. Department of Immunology and Microbial Sciiences, The Scripps Research Institute, La Jolla, California, USA

    Michael B. A. Oldstone

  2. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA

    Hugh Rosen

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Martin, R., Sospedra, M. (2014). Sphingosine-1 Phosphate and Central Nervous System. In: Oldstone, M., Rosen, H. (eds) Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases. Current Topics in Microbiology and Immunology, vol 378. Springer, Cham. https://doi.org/10.1007/978-3-319-05879-5_7

Download citation

Publish with us

Policies and ethics

Search

Navigation