{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:36:15Z","timestamp":1775273775948,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Accumulating evidence has suggested that neuropeptides such as orexin, ghrelin, or oxytocin act centrally in the brain to regulate intestinal barrier function through the vagus nerve. It has been reported that the vagal cholinergic anti\u2010inflammatory pathway was blocked by splenectomy. In the present study, we therefore examined the effect of splenectomy on neuropeptides\u2010induced improvement of increased intestinal permeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Colonic permeability was determined in\u00a0vivo by quantifying the absorbed Evans blue in colonic tissue for 15\u2009min spectrophotometrically in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Splenectomy increased colonic permeability. The increased permeability by splenectomy was significantly blocked by vagal activation induced by carbachol or 2\u2010deoxy\u2010d\u2010glucose which was prevented by atropine, suggesting vagal activation could prevent colonic hyperpermeability in splenectomized rats. In the splenectomized rats, intracisternal injection of orexin, ghrelin, oxytocin, or butyrate failed to inhibit increased colonic permeability while intracisternal glucagon\u2010like peptide\u20101 (GLP\u20101) analogue, liraglutide, potently blocked the increased colonic permeability in a dose\u2010dependent manner. The liraglutide\u2010induced improvement of increased colonic permeability was blocked by atropine in splenectomized rats. Intracisternal injection of GLP\u20101 receptor antagonist attenuated 2\u2010deoxy\u2010d\u2010glucose\u2010induced improvement of colonic hyperpermeability in splenectomized rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present results suggested that the spleen is important in the improvement of intestinal barrier function by brain orexin, ghrelin or oxytocin, and butyrate. On the other hand, GLP\u20101 acts centrally in the brain to improve colonic hyperpermeability in a spleen\u2010independent manner. All these results suggest that dual mechanisms (spleen dependent or independent) may exist for the brain\u2010gut regulation in intestinal barrier function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14949","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T10:07:08Z","timestamp":1729850828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Splenectomy prevents brain orexin, ghrelin, or oxytocin but not GLP\u20101\u2010induced improvement of intestinal barrier function in rats"],"prefix":"10.1111","volume":"37","author":[{"given":"Takuya","family":"Funayama","sequence":"first","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsukasa","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of General Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatomo","family":"Ishioh","sequence":"additional","affiliation":[{"name":"Department of General Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pathology Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihiro","family":"Sumi","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasumichi","family":"Toki","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Hatayama","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayo","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motohiro","family":"Shindo","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-007X","authenticated-orcid":false,"given":"Toshikatsu","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318427"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.08.011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134592"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2022.113914"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2023.148371"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108116"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052362"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529409090435"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.48.137"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001308"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13808"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/joe-18-0441"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01842-0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90833-8"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2021.04.005"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"}],"container-title":["Neurogastroenterology &amp; 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