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We studied the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a POP, and a potent aryl hydrocarbon receptor (AHR) ligand, on the ENS and intestinal motility in mice. C57Bl\/6J mice treated with TCDD (2.4\u2009\u00b5g\/kg body weight) for 8 weeks (once per week) exhibited significant delay in intestinal motility as shown by reduced stool frequency, prolonged intestinal transit time, and a persistence of dye in the jejunum compared to control mice with maximal dye retention in the ileum. TCDD significantly increased Cyp1a1 expression, an AHR target gene, and reduced the total number of neurons and affected nitrergic neurons in cells isolated from WT mice, but not Ahr\u2212\/\u2212 mice. In immortalized fetal enteric neuronal cells, TCDD-induced nuclear translocation of AHR as well as increased Cyp1a1 expression. AHR activation did not affect neuronal proliferation. However, AHR activation resulted in enteric neuronal toxicity, specifically, nitrergic neurons. Our results demonstrate that TCDD adversely affects nitrergic neurons and thereby contributes to delayed intestinal motility. These findings suggest that AHR signaling in the ENS may play a role in modulating TCDD-induced gastrointestinal pathophysiology.<\/jats:p>","DOI":"10.1093\/toxsci\/kfad014","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T05:21:50Z","timestamp":1676092910000},"page":"117-128","source":"Crossref","is-referenced-by-count":8,"title":["Aryl hydrocarbon receptor activation affects nitrergic neuronal survival and delays intestinal motility in mice"],"prefix":"10.1093","volume":"192","author":[{"given":"Anitha","family":"Vijay","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University , University Park, Pennsylvania 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina R","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University , University Park, Pennsylvania 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya M","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University , University Park, Pennsylvania 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary H","family":"Perdew","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University , University Park, Pennsylvania 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanthi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases, Emory University School of Medicine , Atlanta, Georgia, USA"},{"name":"Atlanta VA Medical Center , Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2073-0070","authenticated-orcid":false,"given":"Andrew D","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University , University Park, Pennsylvania 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"2024021622265854600_kfad014-B1","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1053\/j.gastro.2008.02.018","article-title":"Characterization of fetal and postnatal enteric neuronal cell lines with improvement in intestinal neural function","volume":"134","author":"Anitha","year":"2008","journal-title":"Gastroenterology"},{"key":"2024021622265854600_kfad014-B2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1172\/JCI26295","article-title":"GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K\/Akt pathway","volume":"116","author":"Anitha","year":"2006","journal-title":"J. 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