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Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease
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 f...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557815/ https://www.ncbi.nlm.nih.gov/pubmed/31231674 http://dx.doi.org/10.1038/s41531-019-0081-9 |
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author | Coletto, Erika Dolan, John S. Pritchard, Sara Gant, Alex Hikima, Atsuko Jackson, Michael J. Benham, Christopher D. Chaudhuri, K. Ray Rose, Sarah Jenner, Peter Iravani, Mahmoud M. |
author_facet | Coletto, Erika Dolan, John S. Pritchard, Sara Gant, Alex Hikima, Atsuko Jackson, Michael J. Benham, Christopher D. Chaudhuri, K. Ray Rose, Sarah Jenner, Peter Iravani, Mahmoud M. |
author_sort | Coletto, Erika |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6557815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65578152019-06-21 Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease Coletto, Erika Dolan, John S. Pritchard, Sara Gant, Alex Hikima, Atsuko Jackson, Michael J. Benham, Christopher D. Chaudhuri, K. Ray Rose, Sarah Jenner, Peter Iravani, Mahmoud M. NPJ Parkinsons Dis Article 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. Nature Publishing Group UK 2019-06-10 /pmc/articles/PMC6557815/ /pubmed/31231674 http://dx.doi.org/10.1038/s41531-019-0081-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Coletto, Erika Dolan, John S. Pritchard, Sara Gant, Alex Hikima, Atsuko Jackson, Michael J. Benham, Christopher D. Chaudhuri, K. Ray Rose, Sarah Jenner, Peter Iravani, Mahmoud M. Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease |
title | Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease |
title_full | Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease |
title_fullStr | Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease |
title_full_unstemmed | Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease |
title_short | Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease |
title_sort | contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of parkinson’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557815/ https://www.ncbi.nlm.nih.gov/pubmed/31231674 http://dx.doi.org/10.1038/s41531-019-0081-9 |
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