{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:38:59Z","timestamp":1790771939731,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,11,27]],"date-time":"2016-11-27T00:00:00Z","timestamp":1480204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP15171"],"award-info":[{"award-number":["GGP15171"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004740","name":"Fondazione del Monte di Bologna e Ravenna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004740","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK 41301"],"award-info":[{"award-number":["P30 DK 41301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK55530"],"award-info":[{"award-number":["DK55530"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2017,5]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Chronic constipation (CC<\/jats:styled-content>) is a common and severe gastrointestinal complaint in Parkinson's disease (PD<\/jats:styled-content>), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function inPD<\/jats:styled-content>patients with constipation (PD<\/jats:styled-content>\/CC<\/jats:styled-content>) vs bothCC<\/jats:styled-content>and controls.<\/jats:p><\/jats:sec>Methods<\/jats:title>Twenty\u2010ninePD<\/jats:styled-content>\/CC<\/jats:styled-content>and 10 RomeIII<\/jats:styled-content>\u2010definedCC<\/jats:styled-content>patients were enrolled. Twenty asymptomatic age\u2010sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated inPD<\/jats:styled-content>\/CC<\/jats:styled-content>andCC<\/jats:styled-content>patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts fromPD<\/jats:styled-content>\/CC<\/jats:styled-content>,CC<\/jats:styled-content>, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP<\/jats:styled-content>) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. ThemRNA<\/jats:styled-content>expression ofVIP<\/jats:styled-content>and its receptors were also assessed.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Four subgroups ofPD<\/jats:styled-content>\/CC<\/jats:styled-content>patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons\/ganglion betweenPD<\/jats:styled-content>\/CC<\/jats:styled-content>vsCC<\/jats:styled-content>or vs controls. A reduced number of submucosal neurons containingVIP<\/jats:styled-content>immunoreactivity was found inPD<\/jats:styled-content>\/CC<\/jats:styled-content>vs controls (P<<\/jats:italic>.05).VIP<\/jats:styled-content><\/jats:italic>,VIPR<\/jats:styled-content>1<\/jats:italic>, andVIPR<\/jats:styled-content>2<\/jats:italic>mRNA<\/jats:styled-content>expression was significantly reduced inPD<\/jats:styled-content>\/CC<\/jats:styled-content>vsCC<\/jats:styled-content>and controls (P<\/jats:italic><.05).<\/jats:p><\/jats:sec>Conclusions and Inferences<\/jats:title>Colonic motor and rectal sensory functions are impaired in mostPD<\/jats:styled-content>\/CC<\/jats:styled-content>patients. These abnormalities are associated with a decreasedVIP<\/jats:styled-content>expression in submucosal neurons. Both sensory\u2010motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute toPD<\/jats:styled-content>\/CC<\/jats:styled-content>pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12995","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T03:02:42Z","timestamp":1480302162000},"source":"Crossref","is-referenced-by-count":49,"title":["Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation"],"prefix":"10.1111","volume":"29","author":[{"given":"F.","family":"Giancola","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"},{"name":"Department of Veterinary Medical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Torresan","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Repossi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bianco","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"},{"name":"Department of Veterinary Medical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Latorre","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Guarino","sequence":"additional","affiliation":[{"name":"Neurology Unit St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Volta","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Clavenzani","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mazzoni","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Chiocchetti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bazzoli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna, and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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