{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:47:25Z","timestamp":1771051645754,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["(UNIPD-CPDR155591\/15 Assegno di Ricerca 2016"],"award-info":[{"award-number":["(UNIPD-CPDR155591\/15 Assegno di Ricerca 2016"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["UNIPD-DSF-PRID-2017"],"award-info":[{"award-number":["UNIPD-DSF-PRID-2017"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["UNIPD\u2010DSF-DOR-2018 and 2019"],"award-info":[{"award-number":["UNIPD\u2010DSF-DOR-2018 and 2019"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"name":"San Camillo Hospital, Treviso (Italy)","award":["San Camillo Hospital Grant PhD Program 2016-2019 in Pharmacological Sciences"],"award-info":[{"award-number":["San Camillo Hospital Grant PhD Program 2016-2019 in Pharmacological Sciences"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Enteric glial cells (EGCs) influence nitric oxide (NO)\u2212 and adenosine diphosphate (ADP)\u2212 mediated signaling in the enteric nervous system (ENS). Since Toll-like receptor 4 (TLR4) participates to EGC homoeostasis, this study aimed to evaluate the possible involvement of EGCs in the alterations of the inhibitory neurotransmission in TLR4\u2212\/\u2212 mice. Ileal segments from male TLR4\u2212\/\u2212 and wild-type (WT) C57BL\/6J mice were incubated with the gliotoxin fluoroacetate (FA). Alterations in ENS morphology and neurochemical coding were investigated by immunohistochemistry whereas neuromuscular responses were determined by recording non-adrenergic non-cholinergic (NANC) relaxations in isometrically suspended isolated ileal preparations. TLR4\u2212\/\u2212 ileal segments showed increased iNOS immunoreactivity associated with enhanced NANC relaxation, mediated by iNOS-derived NO and sensitive to P2Y1 inhibition. Treatment with FA diminished iNOS immunoreactivity and partially abolished NO\u2212 and ADP\u2212 mediated relaxation in the TLR4\u2212\/\u2212 mouse ileum, with no changes of P2Y1 and connexin-43 immunofluorescence distribution in the ENS. After FA treatment, S100\u03b2 and GFAP immunoreactivity in TLR4\u2212\/\u2212 myenteric plexus was reduced to levels comparable to those observed in WT. Our findings show the involvement of EGCs in the alterations of ENS architecture and in the increased purinergic and nitrergic-mediated relaxation, determining gut dysmotility in TLR4\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.3390\/cells9040838","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T05:52:30Z","timestamp":1585720350000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Involvement of Enteric Glia in Small Intestine Neuromuscular Dysfunction of Toll-Like Receptor 4-Deficient Mice"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-4475","authenticated-orcid":false,"given":"Silvia","family":"Cerantola","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"},{"name":"San Camillo Hospital, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Caputi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"},{"name":"APC Microbiome Ireland, University College Cork, IE5 Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-4183","authenticated-orcid":false,"given":"Ilaria","family":"Marsilio","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Ridolfi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Faggin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Bistoletti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-3441","authenticated-orcid":false,"given":"Cristina","family":"Giaroni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-7965","authenticated-orcid":false,"given":"Maria Cecilia","family":"Giron","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1053\/j.gastro.2014.09.040","article-title":"Enteric glial cells: Recent developments and future directions","volume":"147","author":"Neunlist","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1177\/0394632015599707","article-title":"Enteric glia: A new player in inflammatory bowel diseases","volume":"28","author":"Capoccia","year":"2015","journal-title":"Int. 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