Enteric neurodegeneration in ageing

Abstract

The objective of this article is to review the clinical presentation and neurobiology of degeneration of the enteric nervous system with emphasis on human data where available. Constipation, incontinence and evacuation disorders are frequently encountered in the ageing population. Healthy lower gastrointestinal function is essential for successful ageing as it is critical to maintaining independence and autonomy to pursue further activity. One clinical expression of enteric neurodegeneration is constipation. However, the aetiology may be multifactorial as disturbances of epithelial, muscle or neural function may all result from neurodegeneration. There is evidence of loss of excitatory (e.g. cholinergic) enteric neurons and interstitial cells of Cajal, whereas inhibitory (including nitrergic) neurons appear unaffected. Understanding neurodegeneration in the enteric nervous system is key to developing treatments to reverse it. Neurotrophins have been shown to accelerate colonic transit and relieve constipation in the medium term; they are also implicated in maintenance programmes in adult enteric neurons through a role in antioxidant defence. However, their effects in ageing colon require further study. There is evidence that 5-HT(2) and 5-HT(4) mechanisms are involved in development, maintenance and survival of enteric neurons. Further research is needed to understand and potentially reverse enteric neurodegeneration.

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

“…These symptoms are classified as drooling, pharyngeal or esophageal dysmotility, early satiety and nausea, constipation and defecatory dysfunction, as elegantly summarized in a review by Cerosimo and Benaroch [55]. Chronic constipation most likely reflects a loss of neurons in the myenteric plexus [56,57] and may also occur as a manifestation of the age-related neurodegeneration of the ENS [58]. Thus, reduced colonic transit is likely to reflect the involvement of myenteric neurons in PD [9,50].…”

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

“…PD patients with severe constipation have been reported to present lower levels of GI DA, suggesting that damage to the enteric DAergic system might be an important factor underlying GI dysfunction [99]. More recently, age-related loss of myenteric neurons has been associated with chronic constipation, although studies are widely controversial [100, 101]. Unfortunately, it is still not clear whether PD leads to the loss of enteric neurons.…”

The effects of ageing on the onset and disappearance of unexplained abdominal pain: a population‐based study

“…6, 10 Chronic abdominal pain is the central symptom of irritable bowel syndrome 8 as well as one of the major symptom components of functional dyspepsia. 11 Whether the apparent decrease in IBS and dyspepsia with age is explained by the disappearance of abdominal pain is unknown.…”