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Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate. / Coletto, Erika; Tough, Ian; Pritchard, Sara; Hikima, Atsuko; Jackson, Michael; Jenner, Peter; Chaudhuri, K. Ray; Cox, Helen; Iravani, Mahmoud; Rose, Sarah.

In: npj Parkinson's Disease, Vol. 7, No. 1, 9, 21.01.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Coletto, E, Tough, I, Pritchard, S, Hikima, A, Jackson, M, Jenner, P, Chaudhuri, KR, Cox, H, Iravani, M & Rose, S 2021, 'Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate', npj Parkinson's Disease, vol. 7, no. 1, 9. https://doi.org/10.1038/s41531-020-00150-x

APA

Coletto, E., Tough, I., Pritchard, S., Hikima, A., Jackson, M., Jenner, P., Chaudhuri, K. R., Cox, H., Iravani, M., & Rose, S. (2021). Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate. npj Parkinson's Disease, 7(1), [9]. https://doi.org/10.1038/s41531-020-00150-x

Vancouver

Author

Coletto, Erika ; Tough, Ian ; Pritchard, Sara ; Hikima, Atsuko ; Jackson, Michael ; Jenner, Peter ; Chaudhuri, K. Ray ; Cox, Helen ; Iravani, Mahmoud ; Rose, Sarah. / Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate. In: npj Parkinson's Disease. 2021 ; Vol. 7, No. 1.

Bibtex

@article{bb687364c873424d83b507dccc7e70f9,
title = "Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate",
abstract = "The pathological changes underlying gastrointestinal (GI) dysfunction in Parkinson{\textquoteright}s disease (PD) are poorly understood and the symptoms remain inadequately treated. In this study we compared the functional and neurochemical changes in the enteric nervous system in the colon of adult, L-DOPA-responsive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset, with na{\"i}ve controls. Measurement of mucosal vectorial ion transport, spontaneous longitudinal smooth muscle activity and immunohistochemical assessment of intrinsic innervation were each performed in discrete colonic regions of na{\"i}ve and MPTP-treated marmosets. The basal short circuit current (Isc) was lower in MPTP-treated colonic mucosa while mucosal resistance was unchanged. There was no difference in basal cholinergic tone, however, there was an increased excitatory cholinergic response in MPTP-treated tissues when NOS was blocked with L-Nω-nitroarginine. The amplitude and frequency of spontaneous contractions in longitudinal smooth muscle as well as carbachol-evoked post-junctional contractile responses were unaltered, despite a decrease in choline acetyltransferase and an increase in the vasoactive intestinal polypeptide neuron numbers per ganglion in the proximal colon. There was a low-level inflammation in the proximal but not the distal colon accompanied by a change in α-synuclein immunoreactivity. This study suggests that MPTP treatment produces long-term alterations in colonic mucosal function associated with amplified muscarinic mucosal activity but decreased cholinergic innervation in myenteric plexi and increased nitrergic enteric neurotransmission. This suggests that long-term changes in either central or peripheral dopaminergic neurotransmission may lead to adaptive changes in colonic function resulting in alterations in ion transport across mucosal epithelia that may result in GI dysfunction in PD.",
author = "Erika Coletto and Ian Tough and Sara Pritchard and Atsuko Hikima and Michael Jackson and Peter Jenner and Chaudhuri, {K. Ray} and Helen Cox and Mahmoud Iravani and Sarah Rose",
note = "{\textcopyright} The Author(s) 2021. 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. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.",
year = "2021",
month = jan,
day = "21",
doi = "10.1038/s41531-020-00150-x",
language = "English",
volume = "7",
journal = "npj Parkinson's Disease",
issn = "2373-8057",
publisher = "Springer International Publishing AG, part of Springer Nature ",
number = "1",

}

RIS

TY - JOUR

T1 - Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate

AU - Coletto, Erika

AU - Tough, Ian

AU - Pritchard, Sara

AU - Hikima, Atsuko

AU - Jackson, Michael

AU - Jenner, Peter

AU - Chaudhuri, K. Ray

AU - Cox, Helen

AU - Iravani, Mahmoud

AU - Rose, Sarah

N1 - © The Author(s) 2021. 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. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PY - 2021/1/21

Y1 - 2021/1/21

N2 - The pathological changes underlying gastrointestinal (GI) dysfunction in Parkinson’s disease (PD) are poorly understood and the symptoms remain inadequately treated. In this study we compared the functional and neurochemical changes in the enteric nervous system in the colon of adult, L-DOPA-responsive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset, with naïve controls. Measurement of mucosal vectorial ion transport, spontaneous longitudinal smooth muscle activity and immunohistochemical assessment of intrinsic innervation were each performed in discrete colonic regions of naïve and MPTP-treated marmosets. The basal short circuit current (Isc) was lower in MPTP-treated colonic mucosa while mucosal resistance was unchanged. There was no difference in basal cholinergic tone, however, there was an increased excitatory cholinergic response in MPTP-treated tissues when NOS was blocked with L-Nω-nitroarginine. The amplitude and frequency of spontaneous contractions in longitudinal smooth muscle as well as carbachol-evoked post-junctional contractile responses were unaltered, despite a decrease in choline acetyltransferase and an increase in the vasoactive intestinal polypeptide neuron numbers per ganglion in the proximal colon. There was a low-level inflammation in the proximal but not the distal colon accompanied by a change in α-synuclein immunoreactivity. This study suggests that MPTP treatment produces long-term alterations in colonic mucosal function associated with amplified muscarinic mucosal activity but decreased cholinergic innervation in myenteric plexi and increased nitrergic enteric neurotransmission. This suggests that long-term changes in either central or peripheral dopaminergic neurotransmission may lead to adaptive changes in colonic function resulting in alterations in ion transport across mucosal epithelia that may result in GI dysfunction in PD.

AB - The pathological changes underlying gastrointestinal (GI) dysfunction in Parkinson’s disease (PD) are poorly understood and the symptoms remain inadequately treated. In this study we compared the functional and neurochemical changes in the enteric nervous system in the colon of adult, L-DOPA-responsive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset, with naïve controls. Measurement of mucosal vectorial ion transport, spontaneous longitudinal smooth muscle activity and immunohistochemical assessment of intrinsic innervation were each performed in discrete colonic regions of naïve and MPTP-treated marmosets. The basal short circuit current (Isc) was lower in MPTP-treated colonic mucosa while mucosal resistance was unchanged. There was no difference in basal cholinergic tone, however, there was an increased excitatory cholinergic response in MPTP-treated tissues when NOS was blocked with L-Nω-nitroarginine. The amplitude and frequency of spontaneous contractions in longitudinal smooth muscle as well as carbachol-evoked post-junctional contractile responses were unaltered, despite a decrease in choline acetyltransferase and an increase in the vasoactive intestinal polypeptide neuron numbers per ganglion in the proximal colon. There was a low-level inflammation in the proximal but not the distal colon accompanied by a change in α-synuclein immunoreactivity. This study suggests that MPTP treatment produces long-term alterations in colonic mucosal function associated with amplified muscarinic mucosal activity but decreased cholinergic innervation in myenteric plexi and increased nitrergic enteric neurotransmission. This suggests that long-term changes in either central or peripheral dopaminergic neurotransmission may lead to adaptive changes in colonic function resulting in alterations in ion transport across mucosal epithelia that may result in GI dysfunction in PD.

UR - http://www.scopus.com/inward/record.url?scp=85099966852&partnerID=8YFLogxK

U2 - 10.1038/s41531-020-00150-x

DO - 10.1038/s41531-020-00150-x

M3 - Article

AN - SCOPUS:85099966852

VL - 7

JO - npj Parkinson's Disease

JF - npj Parkinson's Disease

SN - 2373-8057

IS - 1

M1 - 9

ER -