{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T18:51:33Z","timestamp":1785783093040,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":103,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["H2023138"],"award-info":[{"award-number":["H2023138"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Designer receptors exclusively activated by designer drugs (DREADDs)\u2010based chemogenetic tools are commonly used to activate or silence targeted neurons by the agonistic ligand deschloroclozapine (DCZ). This study aimed to establish a Gi\u2010DREADD\u2010based murine model of slow transit constipation (STC) and elucidate its pathophysiological mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adeno\u2010associated virus (AAV) 9\u2010hM4Di was injected into the intestinal wall of mice, and colonic motility was evaluated. The efficiency and immunogenicity of AAV9\u2010hM4Di transduction in the enteric nervous system (ENS) were evaluated. Nitric oxide (NO), acetylcholine (ACh), and substance P (SP) in the colonic tissues and serum samples were analyzed. Calcium (Ca<jats:sup>2+<\/jats:sup>) imaging was performed to evaluate the responses of AAV9\u2010hM4Di on enteric nerves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AAV9\u2010hM4Di\u2010treated mice showed gastrointestinal motility dysfunction, including reduced fecal pellets and decreased fecal mass and water content. Electrophysiological recording of muscle contraction in the isolated colonic tissues from the chemogenetic mice showed decreased frequency and amplitude after DCZ treatment. The mice treated with AAV9\u2010hM4Di showed the highest levels of transduction in the myenteric plexuses of the ENS. There were no differences in transduction in neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT) neurons. Gi\u2010DREADDs significantly downregulated ACh but not NO or SP expression in the distal colon in the chemogenetic mice. Ca<jats:sup>2+<\/jats:sup> transient in neurons of ENS in chemogenetic mice was strongly inhibited by DCZ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>It is feasible to apply the DREADDs\u2010based chemogenetic tools to the ENS. Gi\u2010DREADDs can selectively modulate the ENS, inducing STC without excitatory\u2010neural bias, offering targeted neuromodulation for gastrointestinal motility disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1751-2980.13344","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T07:14:11Z","timestamp":1744614851000},"page":"62-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>DREADDs<\/scp>\u2010Based Chemogenetics Induced Slow Transit Constipation via Inhibition of Enteric Neurons"],"prefix":"10.1111","volume":"26","author":[{"given":"Xin Yi","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing Jiangsu Province China"},{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Xiang","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Institute for Brain Sciences, School of Life Sciences Nanjing University  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Jiang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Qi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-9376","authenticated-orcid":false,"given":"Liang Liang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0381-0773","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Institute for Brain Sciences, School of Life Sciences Nanjing University  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-1091","authenticated-orcid":false,"given":"Ni Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing Jiangsu Province China"},{"name":"Department of Gastroenterology Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.16995"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03376.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.32"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(94)90056-6"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.138.12.1302"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010018\u20102532\u20108"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00472.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701474RR"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.040"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyu007"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.03.065"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12596"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1205295"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2015.08.004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1139152"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1525887"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2019.110715"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2022.112037"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(00)00194-X"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.76"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00081"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.7"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-05843-1_22"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-008-0684-7"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01610-9"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414\u2010431X2023e12466"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10350-004-6251-8"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00264.2021"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03626.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700293104"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010814-124803"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036035"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.3791\/52506"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00554.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i12.1391"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u2010230X\u201013\u201052"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.151"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4106"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3217"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2215"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2016.00070"}],"container-title":["Journal of Digestive Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-2980.13344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T09:02:38Z","timestamp":1745917358000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1751-2980.13344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":42,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/1751-2980.13344"],"URL":"https:\/\/doi.org\/10.1111\/1751-2980.13344","archive":["Portico"],"relation":{},"ISSN":["1751-2972","1751-2980"],"issn-type":[{"value":"1751-2972","type":"print"},{"value":"1751-2980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}