Changes in neuromuscular structure and functions of human colon during ageing are region-dependent
| Autor: | Taher Darreh-Shori, Mohamed A. Thaha, Joanne Chin-Aleong, Alexandra Palmer, M. Jill Saffrey, Joanne E. Martin, John Broad, Shezan Elahi, Shafi Ahmed, Victor W S Kung, Charles H. Knowles, Gareth J. Sanger, Azadeh Karami, Rebecca Carroll |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Contraction (grammar) Neuromuscular Junction Descending colon Neurogastroenterology Tissue Culture Techniques 03 medical and health sciences Colon Ascending 0302 clinical medicine Nerve Fibers Internal medicine Neural Pathways medicine Ascending colon Humans human Myenteric plexus Aged Aged 80 and over colon business.industry Gastroenterology Age Factors axon transport Middle Aged Choline acetyltransferase choline acetyltransferase Electric Stimulation Colon Descending 030104 developmental biology medicine.anatomical_structure Muscle relaxation Endocrinology Ageing ageing Cholinergic 030211 gastroenterology & hepatology Female business Muscle Contraction |
| Zdroj: | Gut |
| ISSN: | 1468-3288 |
| Popis: | ObjectiveTo determine if human colonic neuromuscular functions decline with increasing age.DesignLooking 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.ResultsWith 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.ConclusionIn ascending not descending colon, ageing impairs cholinergic function. |
| Databáze: | OpenAIRE |
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