F Giancola1,2, F Torresan1, R Repossi1, F Bianco1,2, R Latorre1, A Ioannou1, M Guarino3, U Volta1, P Clavenzani2, M Mazzoni2, R Chiocchetti2, F Bazzoli1, R A Travagli4, C Sternini5, R De Giorgio1,6. 1. Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy. 2. Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy. 3. Neurology Unit, St. Orsola-Malpighi Hospital, Bologna, Italy. 4. Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA. 5. CURE Digestive Diseases Research Center, Digestive Diseases Division, Departments of Medicine and Neurobiology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. 6. Centro Unificato di Ricerca Biomedica Applicata, Bologna, Italy.
Abstract
BACKGROUND: Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls. METHODS: Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed. KEY RESULTS: Four subgroups of PD/CC 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 between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05). CONCLUSIONS AND INFERENCES: Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.
BACKGROUND:Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PDpatients with constipation (PD/CC) vs both CC and controls. METHODS: Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed. KEY RESULTS: Four subgroups of PD/CC 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 between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05). CONCLUSIONS AND INFERENCES: Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.
Authors: R Sakakibara; T Odaka; T Uchiyama; M Asahina; K Yamaguchi; T Yamaguchi; T Yamanishi; T Hattori Journal: J Neurol Neurosurg Psychiatry Date: 2003-02 Impact factor: 10.154
Authors: Kaleen M Lavin; Yongchao Ge; Stuart C Sealfon; Venugopalan D Nair; Katarzyna Wilk; Jeremy S McAdam; Samuel T Windham; Preeti Lakshman Kumar; Merry-Lynn N McDonald; Marcas M Bamman Journal: Front Physiol Date: 2020-06-17 Impact factor: 4.566
Authors: Arthur Lionnet; Matthew A Wade; Anne-Gaëlle Corbillé; Alice Prigent; Sébastien Paillusson; Maddalena Tasselli; Jacques Gonzales; Emilie Durieu; Malvyne Rolli-Derkinderen; Emmanuel Coron; Emilie Duchalais; Michel Neunlist; Michael S Perkinton; Diane P Hanger; Wendy Noble; Pascal Derkinderen Journal: Acta Neuropathol Commun Date: 2018-07-23 Impact factor: 7.801