{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T14:52:45Z","timestamp":1758811965221,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Brain\u2010derived neurotrophic factor (BDNF) acts as a neuromodulator to regulate gut motility, but the role of BDNF in diabetes\u2010related dysmotility is uncertain. The aim of this study was to investigate the possible involvement of BDNF and its receptor TrkB in the colonic hypomotility of mice with streptozotocin (STZ)\u2010induced diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single intraperitoneal injection of STZ was used to establish a type 1 diabetes model. An organ bath system was applied to observe the contractile activities of colonic muscle strips. Immunofluorescence and western blotting were performed to evaluate the expression of BDNF and TrkB in the colon. ELISA was used to detect BDNF and SP levels in the serum and colon. The patch\u2010clamp technique was applied to record the currents of L\u2010type calcium channels and large conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels on smooth muscle cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Compared with healthy controls, diabetic mice showed attenuated colonic muscle contraction (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), which was partly reversed by BDNF supplementation. TrkB protein expression was significantly reduced in diabetic mice (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In addition, both BDNF and substance P (SP) levels were decreased, and exogenous administration of BDNF increased SP levels in diabetic mice (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Both the TrkB antagonist and the TrkB antibody inhibited the spontaneous contraction of colonic muscle strips (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Moreover, the BDNF\u2013TrkB signaling system enhanced SP\u2010induced muscle contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Downregulation of BDNF\/TrkB signaling and reduced SP release from the colon may contribute to the colonic hypomotility associated with type 1 diabetes. Brain\u2010derived neurotrophic factor supplementation may have therapeutic potential for diabetes\u2010related constipation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14647","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T10:34:27Z","timestamp":1688726067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Downregulation of <scp>BDNF\u2013TrkB<\/scp> signaling may contribute to the colonic motility disorders in mice with streptozocin\u2010induced diabetes"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-6657","authenticated-orcid":false,"given":"Xiaojing","family":"Quan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 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