Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

Patel, Bhavik Anil; Patel, Nirav; Fidalgo, Sara; Wang, Chunfang; Ranson, Richard N.; Saffrey, M. Jill; Yeoman, Mark

doi:10.1016/j.exger.2014.02.007

Cited by 28 publications

(39 citation statements)

References 42 publications

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“…The myenteric plexus modulates the contractility of the smooth muscles that line the gastrointestinal tract and is fundamental to gut transit. Ageing is associated with a decrease in the total number and density of enteric nerve fibres, particularly in the myenteric plexus [7,25,31,32]. The two major groups of myenteric neurons are cholinergic neurons, which are excitatory, and nitrergic neurons, which are inhibitory.…”

Section: Small Intestinal Digestion and Absorption Of Nutrientsmentioning

confidence: 99%

“…In mice this effect appears, at least in part, to be because of an attenuation of signalling by tachykinin, an important regulator of colonic motility. In older (24 months) compared with younger (3 months) mice, faecal output was reduced primarily because of an increase in transit time, leading to reduction in both the number and water content of pellets produced [31]. In rats, increase in oxidative stress played an important role in the age-associated decrease in internal anal sphincter tone in older (24-30 months) compared with younger (4-6 months) rats and may, therefore, be one of the underlying mechanisms of faecal incontinence [39].…”

Section: Colonic and Anorectal Functionmentioning

confidence: 99%

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The ageing gastrointestinal tract

Soenen

Rayner

Jones

et al. 2016

Current Opinion in Clinical Nutrition and Metabolic Care

185

119

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Alterations in gut function with ageing have particular implications for oesophageal, gastric, and colonic motility. Older individuals are particularly susceptible to malnutrition, postprandial hypotension, dysphagia, constipation, and faecal incontinence. Decrease in the number of nerve cells of the myenteric plexus that impact digestive absorption and the surface area of the small intestine because of degeneration of villi may lead to blunted absorption of nutrients. Impairment of the intestinal immune system as a result of ageing, including the mucosal layer of the gastrointestinal tract, appears to be a significant contributor to the age-related increase in the incidence and severity of infections.

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Section: Small Intestinal Digestion and Absorption Of Nutrientsmentioning

confidence: 99%

Section: Colonic and Anorectal Functionmentioning

confidence: 99%

The ageing gastrointestinal tract

Soenen

Rayner

Jones

et al. 2016

Current Opinion in Clinical Nutrition and Metabolic Care

185

119

View full text Add to dashboard Cite

show abstract

“…Many drugs, disease states, surgery, and aging alter gastrointestinal function, leading to increased or decreased transit in part of or in the entire gastrointestinal tract (Bauer, 2010; Mattei & Rombeau, 2006; Patel, et al, 2014; Siemens, Gaertner, & Becker, 2014; Smits & Lefebvre, 1996). In animal models, methods to measure gastrointestinal function include fecal pellet discharge counts, gastrointestinal emptying, gastrointestinal transit, and large intestinal transit, in vivo or ex vivo (Smits & Lefebvre, 1996; Wehner, et al, 2007; Yang, et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A non-invasive method to evaluate gastrointestinal transit behavior in rat

Bove

2015

Journal of Pharmacological and Toxicological Methods

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Introduction Many factors alter gastrointestinal transit. Animal models are useful for preclinical studies of gastrointestinal transit, but terminal methods do not allow later study, and stressful assessment methods will likely alter the transit of the animal. To overcome these factors, we developed a new method to assay rat total gastrointestinal transit. Methods Standard plastic cages with their bottoms cut off were placed on wire mesh floors. Custom apparatuses were built to contain fecal pellets as they fell through the floors. Webcams connected to a computer running a security program were placed to image the pellets at regular intervals. Custom food was obtained with and without blue pigment. After habituating to the cages and the non-pigmented food, the pigmented food was administered. The duration to the appearance of the first pigmented pellet was determined by reviewing the photographs. This duration represents the complete gastrointestinal behavior, including feeding. We compared 24-hour fecal pellet counts using images to counts by visual inspection, and also made hourly counts. After establishing baseline transit times and hourly fecal pellet discharge, rats were given buprenorphine, known to alter gastrointestinal transit. Transit times and hourly discharge were obtained again and compared to the baselines. Results The methods were successful in determining transit times. Baseline measures were consistent between three groups of 8 rats. Visual and image-based counts were highly correlated. Transit times and hourly pellet discharge were reduced by buprenorphine. Discussion The described method offers a relatively simple, inexpensive, and non-invasive means to measure rat gastrointestinal behaviour. The method has potential for any studies where altered total gastrointestinal transit is an experimental concern.

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“…In summary, we have shown that the natural aging process reduces evoked relaxation in the murine anorectum in the absence of changes in basal tone or excitatory motor neuron signaling. This change is predominantly due to a decrease in nitrergic signaling and may well contribute to an impairment of fecal output with increasing age and contribute to the fecal impaction and constipation phenotype previously described in this model …”

Section: Discussionmentioning

confidence: 66%

“…The effects of age on the properties of both spontaneous and evoked IJPs recorded from anorectum smooth muscle cells were examined in the presence of scopolamine, guanethidine and nifedipine. We focused on the 12 and 24 month age groups as 12 months represented the peak of the EFS/nicotine‐evoked relaxations in the IAS and 24 months, the time point where we had previously demonstrated clear signs of fecal impaction and a constipation phenotype . Intracellular recordings from single muscle cells showed spontaneous miniature inhibitory junction potentials (mIJPs) superimposed on the resting membrane potential (RMP) (Figure Ai).…”

Section: Resultsmentioning

confidence: 99%

Changes in murine anorectum signaling across the life course

Fidalgo

Patel

Ranson

et al. 2018

Neurogastroenterology Motil

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BackgroundIncreasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.MethodsThe effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age‐related changes in nitric oxide and acetylcholine release.Key ResultsNitrergic relaxation increased between 3 and 6 months, peaked at 12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age‐related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age‐related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.Conclusions and InferencesThe decrease in nitrergic signaling with increasing age may contribute to the age‐related fecal impaction and constipation previously described in this model by partially obstructing defecation.

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Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

Cited by 28 publications

References 42 publications

The ageing gastrointestinal tract

The ageing gastrointestinal tract

A non-invasive method to evaluate gastrointestinal transit behavior in rat

Changes in murine anorectum signaling across the life course

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