{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:39:00Z","timestamp":1783075140258,"version":"3.54.6"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction:<\/jats:title>\n                  <jats:p>\u03b17 nicotinic acetylcholine receptors (nAChRs) play an important role in vagus nerve-based cholinergic anti-inflammatory effects. This study was designed to assess the role of \u03b17 nAChRs in dextran sodium sulfate (DSS)-induced colitis in male and female mouse. We first compared disease activity and pathogenesis of colitis in \u03b17 knockout and wild-type mice. We then evaluated the effect of several \u03b17 direct and indirect agonists on the severity of disease in the DSS-induced colitis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>Male and female adult mice were administered 2.5% DSS solution freely in the drinking water for 7 consecutive days and the colitis severity (disease activity index) was evaluated as well as colon length, colon histology, and levels of tumor necrosis factor-alpha colonic levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Male, but not female, \u03b17 knockout mice displayed a significantly increased colitis severity and higher tumor necrosis factor-alpha levels as compared with their littermate wild-type mice. Moreover, pretreatment with selective \u03b17 ligands PHA-543613, choline, and PNU-120596 decreased colitis severity in male but not female mice. The anti-colitis effects of these \u03b17 compounds dissipated when administered at higher doses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Our results suggest the presence of a \u03b17-dependent anti-colitis endogenous tone in male mice. Finally, our results show for the first time that female mice are less sensitive to the anti-colitis activity of \u03b17 agonists. Ovarian hormones may play a key role in the sex difference effect of \u03b17 nAChRs modulation of colitis in the mouse.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications:<\/jats:title>\n                  <jats:p>Our collective results suggest that targeting \u03b17 nAChRs could represent a viable therapeutic approach for intestinal inflammation diseases such as ulcerative colitis with the consideration of sex differences.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ntr\/ntw245","type":"journal-article","created":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T20:08:43Z","timestamp":1474142923000},"page":"460-468","source":"Crossref","is-referenced-by-count":23,"title":["Sex Differences and Drug Dose Influence the Role of the \u03b17 Nicotinic Acetylcholine Receptor in the Mouse Dextran Sodium Sulfate-Induced Colitis Model"],"prefix":"10.1093","volume":"19","author":[{"given":"Shakir D.","family":"AlSharari","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, King Saud University, Riyadh, Saudi Arabia;"},{"name":"Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Bagdas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA;"},{"name":"Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid I.","family":"Akbarali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patraic A.","family":"Lichtman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erinn S.","family":"Raborn","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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