title: Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.|Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Giancola
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Torresan
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Repossi
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.|Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bianco
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Latorre
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ioannou
authors.affiliation: Neurology Unit, St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Guarino
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Volta
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Clavenzani
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mazzoni
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Chiocchetti
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bazzoli
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Travagli
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Sternini
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy.|Centro Unificato di Ricerca Biomedica Applicata, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Giorgio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059329:Cholinergic Neurons / Q000378:metabolism; D002908:Chronic Disease; D003248:Constipation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D005260:Female; D005772:Gastrointestinal Transit; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D012002:Rectal Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D013368:Submucous Plexus / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide
keywords: anorectal manometry; cholinergic neurons; secretomotor neurons; slow transit constipation