{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:27:38Z","timestamp":1791473258265,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T00:00:00Z","timestamp":1523404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31DK108540 to ETS"],"award-info":[{"award-number":["F31DK108540 to ETS"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK113800 to GMM"],"award-info":[{"award-number":["R01DK113800 to GMM"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS069628"],"award-info":[{"award-number":["NS069628"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS095007"],"award-info":[{"award-number":["NS095007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI128595"],"award-info":[{"award-number":["AI128595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS076200"],"award-info":[{"award-number":["NS076200"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS095007"],"award-info":[{"award-number":["NS095007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["P20 RR16435"],"award-info":[{"award-number":["P20 RR16435"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG5170A6"],"award-info":[{"award-number":["RG5170A6"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["PP2248"],"award-info":[{"award-number":["PP2248"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Multiple sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>) is an autoimmune disease of the central nervous system that, in addition to motor, sensory, and cognitive symptoms, also causes constipation, which is poorly understood. Here, we characterize gastrointestinal (<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>) dysmotility in the experimental autoimmune encephalomyelitis (<jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>) mouse model of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and evaluate whether autoantibodies target the enteric nervous system (<jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content>) and cause dysmotility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> was induced in male <jats:styled-content style=\"fixed-case\">SJL<\/jats:styled-content> and B6 mice. <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> motility was assessed <jats:italic>in vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> in wild type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) and B cell\u2010deficient mice. <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> serum was used to survey potential targets in the <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content> and changes in the <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content> structure were characterized using immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> mice developed accelerated gastric emptying and delayed whole <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> transit with reduced colonic motility. Fecal water content was reduced, and colonic migrating myoelectrical complexes (<jats:styled-content style=\"fixed-case\">CMMC<\/jats:styled-content>) and slow waves were less frequent. Colons from <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> mice exhibited decreased <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content> levels in glia. Sera from <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients and from <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> mice targeted <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content> neurons and glia. B\u2010cell deficiency in <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> protected against colonic dysmotility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Consistent with symptoms experienced in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>, we demonstrate that <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> mice widely exhibit features of <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> dysmotility that persisted in the absence of extrinsic innervation, suggesting direct involvement of <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content> neurocircuitry. The absence of <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> dysmotility in B cell\u2010deficient mice with <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> together with <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> serum immunoreactivity against <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content> targets suggests that <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> could be classified among other diseases known to induce autoimmune <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> dysmotility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13349","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T05:05:33Z","timestamp":1523509533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis"],"prefix":"10.1111","volume":"30","author":[{"given":"E. T.","family":"Spear","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A.","family":"Holt","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. M.","family":"Haag","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Mawe","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. W.","family":"Hennig","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"},{"name":"Department of Pharmacology The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Lavoie","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Applebee","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Teuscher","sequence":"additional","affiliation":[{"name":"Department of Medicine The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-8468","authenticated-orcid":false,"given":"G. M.","family":"Mawe","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences The University of Vermont  Burlington VT USA"},{"name":"Department of Pharmacology The University of Vermont  Burlington VT USA"},{"name":"Department of Medicine The University of Vermont  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00887825"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)91087-M"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/0016-5085(83)90414-6","article-title":"Gastrointestinal dysfunction in multiple sclerosis","volume":"84","author":"Sullivan SN","year":"1983","journal-title":"Gastroenterology"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004150050508"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00900497"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.60.1.31"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S0016-5085(82)80066-8","article-title":"Colonic dysfunction in multiple sclerosis","volume":"83","author":"Glick ME","year":"1982","journal-title":"Gastroenterology"},{"key":"e_1_2_9_9_1","volume-title":"The enteric nervous system","author":"Furness JB","year":"2006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.61.1.117"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/286736a0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22876"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76306"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.061"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2626"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.04.009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-30791-5_6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.12.015"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.5.629"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022328"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2010.01393.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.9.1372"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514522104"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12072"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1742-6"},{"issue":"1","key":"e_1_2_9_26_1","first-page":"5","article-title":"Evidence for antibodies targeting the enteric nervous system in multiple sclerosis","volume":"28","author":"Spear ET","year":"2016","journal-title":"Neurogastroenterol. Motil"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.4049\/jimmunol.161.4.1860","article-title":"New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice","volume":"161","author":"Butterfield RJ","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600536103"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-272542"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e328361eaf8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00399.2009"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2005\/103615"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-11-3"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2006.04.027"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.067595"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38216"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00664-4"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13292"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4103\/2319-4170.155590"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.13349","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T01:15:31Z","timestamp":1694999731000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,11]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/nmo.13349"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13349","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,11]]},"assertion":[{"value":"2018-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13349"}}