Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation

F. Giancola, F. Torresan, R. Repossi, F. Bianco, R. Latorre, A. Ioannou, M. Guarino, U. Volta, P. Clavenzani, M. Mazzoni, R. Chiocchetti, F. Bazzoli, R. A. Travagli, C. Sternini, R. De Giorgio

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere12995
JournalNeurogastroenterology and Motility
Volume29
Issue number5
DOIs
StatePublished - May 2017

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Vasoactive Intestinal Peptide
Constipation
Parkinson Disease
Down-Regulation
Neurons
Manometry
Messenger RNA
Choline O-Acetyltransferase
Colonoscopy

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Giancola, F., Torresan, F., Repossi, R., Bianco, F., Latorre, R., Ioannou, A., ... De Giorgio, R. (2017). Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation. Neurogastroenterology and Motility, 29(5), [e12995]. https://doi.org/10.1111/nmo.12995
Giancola, F. ; Torresan, F. ; Repossi, R. ; Bianco, F. ; Latorre, R. ; Ioannou, A. ; Guarino, M. ; Volta, U. ; Clavenzani, P. ; Mazzoni, M. ; Chiocchetti, R. ; Bazzoli, F. ; Travagli, R. A. ; Sternini, C. ; De Giorgio, R. / Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation. In: Neurogastroenterology and Motility. 2017 ; Vol. 29, No. 5.
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title = "Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation",
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.",
author = "F. Giancola and F. Torresan and R. Repossi and F. Bianco and R. Latorre and A. Ioannou and M. Guarino and U. Volta and P. Clavenzani and M. Mazzoni and R. Chiocchetti and F. Bazzoli and Travagli, {R. A.} and C. Sternini and {De Giorgio}, R.",
year = "2017",
month = "5",
doi = "10.1111/nmo.12995",
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volume = "29",
journal = "Neurogastroenterology and Motility",
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Giancola, F, Torresan, F, Repossi, R, Bianco, F, Latorre, R, Ioannou, A, Guarino, M, Volta, U, Clavenzani, P, Mazzoni, M, Chiocchetti, R, Bazzoli, F, Travagli, RA, Sternini, C & De Giorgio, R 2017, 'Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation', Neurogastroenterology and Motility, vol. 29, no. 5, e12995. https://doi.org/10.1111/nmo.12995

Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation. / Giancola, F.; Torresan, F.; Repossi, R.; Bianco, F.; Latorre, R.; Ioannou, A.; Guarino, M.; Volta, U.; Clavenzani, P.; Mazzoni, M.; Chiocchetti, R.; Bazzoli, F.; Travagli, R. A.; Sternini, C.; De Giorgio, R.

In: Neurogastroenterology and Motility, Vol. 29, No. 5, e12995, 05.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation

AU - Giancola, F.

AU - Torresan, F.

AU - Repossi, R.

AU - Bianco, F.

AU - Latorre, R.

AU - Ioannou, A.

AU - Guarino, M.

AU - Volta, U.

AU - Clavenzani, P.

AU - Mazzoni, M.

AU - Chiocchetti, R.

AU - Bazzoli, F.

AU - Travagli, R. A.

AU - Sternini, C.

AU - De Giorgio, R.

PY - 2017/5

Y1 - 2017/5

N2 - 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.

AB - 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.

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U2 - 10.1111/nmo.12995

DO - 10.1111/nmo.12995

M3 - Article

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AN - SCOPUS:85005810438

VL - 29

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

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