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Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease : contractile dysfunction in MPTP-treated primate ileum. / Coletto, E; Dolan, John S; Pritchard, Sara; Gant, Alex; Hikima, Atsuko; Jackson, Michael J; Benham, Christopher; Chaudhuri, K. Ray; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud.

In: npj Parkinson's Disease, Vol. 5, No. 10, 10.06.2019, p. 1-12.

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Coletto, E ; Dolan, John S ; Pritchard, Sara ; Gant, Alex ; Hikima, Atsuko ; Jackson, Michael J ; Benham, Christopher ; Chaudhuri, K. Ray ; Rose, Sarah ; Jenner, Peter ; Iravani, Mahmoud. / Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease : contractile dysfunction in MPTP-treated primate ileum. In: npj Parkinson's Disease. 2019 ; Vol. 5, No. 10. pp. 1-12.

Bibtex

@article{5f2cfe85bc6c48ff9296043683f34a23,
title = "Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson{\textquoteright}s disease: contractile dysfunction in MPTP-treated primate ileum",
abstract = "Bowel dysfunction is a common non-motor symptom in Parkinson's disease (PD). The main contractile neurotransmitter in the GI tract is acetylcholine (ACh), while nitric oxide (NO) causes the relaxation of smooth muscle in addition to modulating ACh release. The aim of this study was to characterise functional and neurochemical changes in the isolated ileum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmoset, an established model of PD motor dysfunction. While NO-synthase inhibitor L-NAME concentration dependently augmented the neurogenically-evoked contractions and inhibited the relaxations in normal tissues, it had no effects on the MPTP ileum. Immunohistochemical analyses of the myenteric plexus showed that ChAT-immunoreactivity (-ir) was significantly reduced and the density of the enteric glial cells as shown by SOX-10-ir was increased. However, no change in TH-, 5-HT-, VIP- or nNOS-ir was observed in the MPTP tissues. The enhancement of the neurogenically-evoked contractions and the inhibition of the relaxation phase by L-NAME in the control tissues is in line with NO's direct relaxing effect on smooth muscle and its indirect inhibitory effect on ACh release. The absence of the relaxation and the inefficacy of L-NAME in the MPTP tissues suggests that central dopaminergic loss dopamine may eventually lead to the impairment of NO signal coupling that affects bowel function, and this may be the result of a complex dysregulation at the level of the neuroeffector junction.",
keywords = "Parkinson Disease, Gastrointestinal Tract",
author = "E Coletto and Dolan, {John S} and Sara Pritchard and Alex Gant and Atsuko Hikima and Jackson, {Michael J} and Christopher Benham and Chaudhuri, {K. Ray} and Sarah Rose and Peter Jenner and Mahmoud Iravani",
year = "2019",
month = jun,
day = "10",
doi = "10.1038/s41531-019-0081-9",
language = "English",
volume = "5",
pages = "1--12",
journal = "npj Parkinson's Disease",
issn = "2373-8057",
publisher = "Springer International Publishing AG, part of Springer Nature ",
number = "10",

}

RIS

TY - JOUR

T1 - Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease

T2 - contractile dysfunction in MPTP-treated primate ileum

AU - Coletto, E

AU - Dolan, John S

AU - Pritchard, Sara

AU - Gant, Alex

AU - Hikima, Atsuko

AU - Jackson, Michael J

AU - Benham, Christopher

AU - Chaudhuri, K. Ray

AU - Rose, Sarah

AU - Jenner, Peter

AU - Iravani, Mahmoud

PY - 2019/6/10

Y1 - 2019/6/10

N2 - Bowel dysfunction is a common non-motor symptom in Parkinson's disease (PD). The main contractile neurotransmitter in the GI tract is acetylcholine (ACh), while nitric oxide (NO) causes the relaxation of smooth muscle in addition to modulating ACh release. The aim of this study was to characterise functional and neurochemical changes in the isolated ileum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmoset, an established model of PD motor dysfunction. While NO-synthase inhibitor L-NAME concentration dependently augmented the neurogenically-evoked contractions and inhibited the relaxations in normal tissues, it had no effects on the MPTP ileum. Immunohistochemical analyses of the myenteric plexus showed that ChAT-immunoreactivity (-ir) was significantly reduced and the density of the enteric glial cells as shown by SOX-10-ir was increased. However, no change in TH-, 5-HT-, VIP- or nNOS-ir was observed in the MPTP tissues. The enhancement of the neurogenically-evoked contractions and the inhibition of the relaxation phase by L-NAME in the control tissues is in line with NO's direct relaxing effect on smooth muscle and its indirect inhibitory effect on ACh release. The absence of the relaxation and the inefficacy of L-NAME in the MPTP tissues suggests that central dopaminergic loss dopamine may eventually lead to the impairment of NO signal coupling that affects bowel function, and this may be the result of a complex dysregulation at the level of the neuroeffector junction.

AB - Bowel dysfunction is a common non-motor symptom in Parkinson's disease (PD). The main contractile neurotransmitter in the GI tract is acetylcholine (ACh), while nitric oxide (NO) causes the relaxation of smooth muscle in addition to modulating ACh release. The aim of this study was to characterise functional and neurochemical changes in the isolated ileum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmoset, an established model of PD motor dysfunction. While NO-synthase inhibitor L-NAME concentration dependently augmented the neurogenically-evoked contractions and inhibited the relaxations in normal tissues, it had no effects on the MPTP ileum. Immunohistochemical analyses of the myenteric plexus showed that ChAT-immunoreactivity (-ir) was significantly reduced and the density of the enteric glial cells as shown by SOX-10-ir was increased. However, no change in TH-, 5-HT-, VIP- or nNOS-ir was observed in the MPTP tissues. The enhancement of the neurogenically-evoked contractions and the inhibition of the relaxation phase by L-NAME in the control tissues is in line with NO's direct relaxing effect on smooth muscle and its indirect inhibitory effect on ACh release. The absence of the relaxation and the inefficacy of L-NAME in the MPTP tissues suggests that central dopaminergic loss dopamine may eventually lead to the impairment of NO signal coupling that affects bowel function, and this may be the result of a complex dysregulation at the level of the neuroeffector junction.

KW - Parkinson Disease

KW - Gastrointestinal Tract

U2 - 10.1038/s41531-019-0081-9

DO - 10.1038/s41531-019-0081-9

M3 - Article

VL - 5

SP - 1

EP - 12

JO - npj Parkinson's Disease

JF - npj Parkinson's Disease

SN - 2373-8057

IS - 10

ER -