Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier.

Autor:	Ioannou A; Gastroenterology Department, 'Alexandra' General Hospital of Athens, Greece (Alexandros Ioannou)., Costanzini A; Department of Translational Medicine, University of Ferrara, Italy (Anna Costanzini, Lisa Lungaro, Francesca Manza, Matteo Guarino, Giacomo Caio, Roberto De Giorgio)., Giancola F; IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola-Malpighi, Bologna, Italy (Fiorella Giancola)., Cabanillas L; Division of Digestive Diseases, Departments Medicine and Neurobiology, David Geffen School of Medicine, UCLA, Los Angeles, USA (Luis Cabanillas, Catia Sternini)., Lungaro L; Department of Translational Medicine, University of Ferrara, Italy (Anna Costanzini, Lisa Lungaro, Francesca Manza, Matteo Guarino, Giacomo Caio, Roberto De Giorgio)., Manza F; Department of Translational Medicine, University of Ferrara, Italy (Anna Costanzini, Lisa Lungaro, Francesca Manza, Matteo Guarino, Giacomo Caio, Roberto De Giorgio)., Guarino M; Department of Translational Medicine, University of Ferrara, Italy (Anna Costanzini, Lisa Lungaro, Francesca Manza, Matteo Guarino, Giacomo Caio, Roberto De Giorgio)., Arena R; Gastroenterology and Digestive Endoscopy O.U., Azienda Ospedaliero-Universitaria di Ferrara, Italy (Rosario Arena)., Caio G; Department of Translational Medicine, University of Ferrara, Italy (Anna Costanzini, Lisa Lungaro, Francesca Manza, Matteo Guarino, Giacomo Caio, Roberto De Giorgio).; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital-Harvard Medical School, Boston, USA (Giacomo Caio)., Torresan F; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola-Malpighi, Bologna, Italy (Francesco Torresan)., Polydorou A; Department of Surgery, Aretaieion University Hospital, National and Kapodistrian University of Athens, Greece (Andreas Polydorou, Antonios Vezakis)., Vezakis A; Department of Surgery, Aretaieion University Hospital, National and Kapodistrian University of Athens, Greece (Andreas Polydorou, Antonios Vezakis)., Karamanolis G; Gastroenterology Unit, Second Department of Surgery, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece (George Karamanolis)., Sternini C; Division of Digestive Diseases, Departments Medicine and Neurobiology, David Geffen School of Medicine, UCLA, Los Angeles, USA (Luis Cabanillas, Catia Sternini)., De Giorgio R; Department of Translational Medicine, University of Ferrara, Italy (Anna Costanzini, Lisa Lungaro, Francesca Manza, Matteo Guarino, Giacomo Caio, Roberto De Giorgio).
Jazyk:	angličtina
Zdroj:	Annals of gastroenterology [Ann Gastroenterol] 2024 Jan-Feb; Vol. 37 (1), pp. 22-30. Date of Electronic Publication: 2023 Dec 23.
DOI:	10.20524/aog.2023.0851
Abstrakt:	Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities. Competing Interests: Conflict of Interest: None (Copyright: © Hellenic Society of Gastroenterology.)
Databáze:	MEDLINE
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