{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:00:59Z","timestamp":1789736459116,"version":"4.0.1"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T00:00:00Z","timestamp":1295395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21 NS049014"],"award-info":[{"award-number":["R21 NS049014"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG3951A7\/1"],"award-info":[{"award-number":["RG3951A7\/1"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["TR3762-A-1"],"award-info":[{"award-number":["TR3762-A-1"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fingolimod (FTY720) is a sphingosine 1\u2010phosphate (S1P) receptor modulator that regulates lymphocyte trafficking and exerts pleiotropic actions on oligodendrocytes (OLGs) and other neural cells. The purpose of this study was to investigate the role of S1P receptors in a non\u2010T\u2010cell model of demyelination, the cuprizone (cupr) model in C57BL\/6 mice. Treatment with FTY720 (1 mg\/kg) led to attenuated injury to OLGs, myelin, and axons in the corpus callosum (percentage of myelinated fibers was 44.7% in cupr\u2010water and 63% in cupr\u2010FTY720). Reactive astrogliosis and microgliosis were ameliorated when FTY720 was given from d 1, but astrogliosis was augmented when FTY720 was given from wk 4\u20139. FTY720 did not promote remyelination in this model. The protective effect of FTY720 was associated with decreased interleukin\u20101 \u03b2 and CCL2 transcripts in the corpus callosum, as well as altered S1P1 expression. Targeted deletion of S1P1 in OLG lineage cells did not lead to obvious clinical phenotype, but resulted in subtle abnormalities in myelin and an increased susceptibility to cupr\u2010induced demyelination. We conclude that S1P receptors expressed by neuroglia are involved in regulating the response to injury, and CNS effects of FTY720 could contribute to its favorable therapeutic response in multiple sclerosis.\u2014Kim, H. J., Miron, V. E., Dukala, D., Proia, R. L., Ludwin, S. K., Traka, M., Antel, J. P., Soliven, B. Neurobiological effects of sphingosine 1\u2010phosphate receptor modulation in the cuprizone model.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 1509\u20131518 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-173203","type":"journal-article","created":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T23:01:33Z","timestamp":1295478093000},"page":"1509-1518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Neurobiological effects of sphingosine 1\u2010phosphate receptor modulation in the cuprizone model"],"prefix":"10.1096","volume":"25","author":[{"given":"Hye Jung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Neurology University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique E.","family":"Miron","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Dukala","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Proia","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Branch National Institutes of Health Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel K.","family":"Ludwin","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Traka","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack P.","family":"Antel","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Soliven","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,1,19]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"397","article-title":"Sphingosine-1-phosphate: an enigmatic signalling lipid","volume":"4","author":"Spiegel S.","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200176200"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.045658"},{"key":"e_1_2_6_5_1","first-page":"108","article-title":"Sphin-gosine 1-phosphate receptor agonists attenuate relapsing\u2010remitting experimental autoimmune encephalitis in SJL mice","volume":"153","author":"Webb M.","year":"2004","journal-title":"J. Neu-roimmunol."},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2007.06.023"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909494"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907839"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070238"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0910fje"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00374-6"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1269"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.07.006"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307687200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.127183"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)03527-3"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01585.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04629.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21021"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10297"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1096\/fj.06-7420com","article-title":"Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration","volume":"21","author":"Novgorodov A. S.","year":"2007","journal-title":"FASEB"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-17-07458.1999"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00145.2002"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4645-04.2005"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20576"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.123927"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21227"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080478"},{"key":"e_1_2_6_29_1","first-page":"597","article-title":"Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cupri\u2010zone toxicity","volume":"39","author":"Ludwin S. K.","year":"1978","journal-title":"Lab. Invest."},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00168-4"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20000801)61:3<251::AID-JNR3>3.0.CO;2-W"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1998.0715"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00879.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp337"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0460"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn738"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20067"},{"key":"e_1_2_6_39_1","unstructured":"Sidman R. L. Kosaras B. Misra B. M. andSenft S. L.(1999)High-resolution mouse brain atlas.http:\/\/www.hms.harvard.edu\/research\/brain"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4453-08.2008"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.02.004"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.09.069"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2003.10.014"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05703.2000"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-008-9792-8"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.5.1894"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.6.713"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2003.09.003"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091234"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2008.0840"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060783"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.06.034"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn126"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014154108"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20324"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10180"},{"key":"e_1_2_6_57_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neuroscience.2009.12.020","article-title":"Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia","volume":"166","author":"Nayak D.","journal-title":"Neuroscience"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-18-07046.2001"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00279-X"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181587d46"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80093-8"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610318200"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.173"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.10-173203","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.10-173203","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.10-173203","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:38:11Z","timestamp":1761701891000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.10-173203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,19]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1096\/fj.10-173203"],"URL":"https:\/\/doi.org\/10.1096\/fj.10-173203","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,19]]},"assertion":[{"value":"2010-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-01-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}