{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:40:20Z","timestamp":1775868020808,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,4]],"date-time":"2018-11-04T00:00:00Z","timestamp":1541289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Yale Department of Surgery Ohse Research Grant Program"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Knock\u2010out of serotonin re\u2010uptake transporters (SERT) or use of selective serotonin re\u2010uptake inhibitors (SSRIs) potentiates enteric serotonin (5\u2010HT) signaling and stimulates enterocyte proliferation. We hypothesized that increased serotonin signaling would mitigate epithelial injury from intestinal ischemia and reperfusion (I\/R).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice lacking SERT (SERTKO mice) and wild\u2010type littermates (WTLM) were subjected to intestinal ischemia by superior mesenteric artery (SMA) occlusion. At intervals post\u2010laparotomy with or without ischemia, ileum was harvested and prepared for staining. A WTLM subgroup treated with SSRI after SMA occlusion followed by reperfusion was also sacrificed and analyzed. Mucosal injury was scored, percentage of injured villi calculated, and enterocyte proliferation measured. Lastly, staining for enterocytes, enteroendocrine cells, and goblet cells, villus epithelial cellular make\u2010up was investigated at baseline and 14\u00a0days after injury. Measurements were compared between groups using <jats:italic>t<\/jats:italic> test and chi\u2010squared test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>Mucosal injury after I\/R was significantly decreased in SERTKO and SSRI\u2010treated mice compared to WTLM at all intervals except baseline. Enterocyte proliferation was greater in SERTKO and SSRI\u2010treated mice without alteration in cellular composition along villi (<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and inferences<\/jats:title><jats:p>Potentiation of 5\u2010HT signaling is associated with mucosal protection from intestinal I\/R injury without alterations in villus cell distribution, possibly via increased rates of enterocyte renewal.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13498","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T05:25:05Z","timestamp":1541395505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potentiation of serotonin signaling protects against intestinal ischemia and reperfusion injury in mice"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7655-2096","authenticated-orcid":false,"given":"John J.","family":"Tackett","sequence":"first","affiliation":[{"name":"Department of Surgery Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeru","family":"Gandotra","sequence":"additional","affiliation":[{"name":"Department of Surgery Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela C.","family":"Bamdad","sequence":"additional","affiliation":[{"name":"Department of Surgery Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor D.","family":"Muise","sequence":"additional","affiliation":[{"name":"Department of Surgery Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Cowles","sequence":"additional","affiliation":[{"name":"Department of Surgery Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.2004.023846"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181819007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mog.0000153315.28327.6e"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604253341707"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"87","article-title":"Calcium signaling pathways in the enteric nervous system","volume":"1","author":"Turner DJ","year":"1999","journal-title":"Int J Surg Investig"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.11.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.05.007"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00055.2008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00435.2001"},{"issue":"2","key":"e_1_2_10_11_1","first-page":"G339","article-title":"Identification of a 5\u2010hydroxytryptamine (5\u2010HT2) receptor on guinea pig small intestinal crypt cells","volume":"265","author":"Siriwardena AK","year":"1993","journal-title":"The American journal of physiology"},{"issue":"5","key":"e_1_2_10_12_1","first-page":"1123","article-title":"Serotonin receptors influencing cell proliferation in the jejunal crypt epithelium and in colonic adenocarcinomas","volume":"6","author":"Tutton PJ","year":"1986","journal-title":"Anticancer research"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1998.00328.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197012032832302"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0016-5085(61)80133-9","article-title":"Blood serotonin in nontropical sprue","volume":"40","author":"Pimparkar BD","year":"1961","journal-title":"Gastroenterology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(94)90249-6"},{"key":"e_1_2_10_17_1","volume-title":"Textbook of Gastroenterology","author":"Alpers DH","year":"2003"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00065.2010"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69052096.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.132"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00215.2017"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90685.2008"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041867"}],"container-title":["Neurogastroenterology &amp; 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