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Changes in neuromuscular structure and functions of human colon during ageing are region-dependent

OBJECTIVE: To determine if human colonic neuromuscular functions decline with increasing age. DESIGN: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxati...

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Autores principales: Broad, John, Kung, Victor W S, Palmer, Alexandra, Elahi, Shezan, Karami, Azadeh, Darreh-Shori, Taher, Ahmed, Shafi, Thaha, Mohamed Adhnan, Carroll, Rebecca, Chin-Aleong, Joanne, Martin, Joanne E, Saffrey, M Jill, Knowles, Charles H, Sanger, Gareth John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594449/
https://www.ncbi.nlm.nih.gov/pubmed/30228216
http://dx.doi.org/10.1136/gutjnl-2018-316279
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author Broad, John
Kung, Victor W S
Palmer, Alexandra
Elahi, Shezan
Karami, Azadeh
Darreh-Shori, Taher
Ahmed, Shafi
Thaha, Mohamed Adhnan
Carroll, Rebecca
Chin-Aleong, Joanne
Martin, Joanne E
Saffrey, M Jill
Knowles, Charles H
Sanger, Gareth John
author_facet Broad, John
Kung, Victor W S
Palmer, Alexandra
Elahi, Shezan
Karami, Azadeh
Darreh-Shori, Taher
Ahmed, Shafi
Thaha, Mohamed Adhnan
Carroll, Rebecca
Chin-Aleong, Joanne
Martin, Joanne E
Saffrey, M Jill
Knowles, Charles H
Sanger, Gareth John
author_sort Broad, John
collection PubMed
description OBJECTIVE: To determine if human colonic neuromuscular functions decline with increasing age. DESIGN: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35–91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35–60 years) groups. RESULTS: With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon. CONCLUSION: In ascending not descending colon, ageing impairs cholinergic function.
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spelling pubmed-65944492019-07-11 Changes in neuromuscular structure and functions of human colon during ageing are region-dependent Broad, John Kung, Victor W S Palmer, Alexandra Elahi, Shezan Karami, Azadeh Darreh-Shori, Taher Ahmed, Shafi Thaha, Mohamed Adhnan Carroll, Rebecca Chin-Aleong, Joanne Martin, Joanne E Saffrey, M Jill Knowles, Charles H Sanger, Gareth John Gut Neurogastroenterology OBJECTIVE: To determine if human colonic neuromuscular functions decline with increasing age. DESIGN: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35–91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35–60 years) groups. RESULTS: With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon. CONCLUSION: In ascending not descending colon, ageing impairs cholinergic function. BMJ Publishing Group 2019-07 2018-09-18 /pmc/articles/PMC6594449/ /pubmed/30228216 http://dx.doi.org/10.1136/gutjnl-2018-316279 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Neurogastroenterology
Broad, John
Kung, Victor W S
Palmer, Alexandra
Elahi, Shezan
Karami, Azadeh
Darreh-Shori, Taher
Ahmed, Shafi
Thaha, Mohamed Adhnan
Carroll, Rebecca
Chin-Aleong, Joanne
Martin, Joanne E
Saffrey, M Jill
Knowles, Charles H
Sanger, Gareth John
Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
title Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
title_full Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
title_fullStr Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
title_full_unstemmed Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
title_short Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
title_sort changes in neuromuscular structure and functions of human colon during ageing are region-dependent
topic Neurogastroenterology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594449/
https://www.ncbi.nlm.nih.gov/pubmed/30228216
http://dx.doi.org/10.1136/gutjnl-2018-316279
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