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Modeling Age-Associated Neurodegenerative Diseases in Caenorhabditis elegans

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Enteric neurodegeneration in ageing.

M Camilleri¹, T Cowen, T R Koch

¹Departments of Medicine and Physiology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. camilleri.michael@mayo.edu

Neurogastroenterology and Motility

|February 9, 2008

Summary

Degeneration of the enteric nervous system, a cause of constipation in older adults, involves loss of excitatory neurons. Research into neurotrophins and 5-HT mechanisms may offer future treatments.

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Area of Science:

Neuroscience
Gastroenterology
Gerontology

Background:

Ageing is associated with increased prevalence of constipation, incontinence, and evacuation disorders.
Healthy lower gastrointestinal function is crucial for maintaining independence and autonomy in the elderly.
Enteric neurodegeneration contributes to functional gastrointestinal disorders, impacting quality of life.

Purpose of the Study:

To review the clinical presentation and neurobiology of enteric nervous system degeneration.
To emphasize human data regarding enteric neurodegeneration and its impact on ageing.
To explore potential therapeutic targets for reversing enteric neurodegeneration.

Main Methods:

Literature review focusing on clinical presentation and neurobiology of enteric nervous system degeneration.
Emphasis on human data and available research findings.
Analysis of mechanisms involving neurons, interstitial cells of Cajal, and neurotrophic factors.

Main Results:

Constipation is a clinical manifestation of enteric neurodegeneration, often multifactorial.
Evidence suggests loss of excitatory (cholinergic) enteric neurons and interstitial cells of Cajal.
Inhibitory (nitrergic) neurons appear unaffected in this process.
Neurotrophins may accelerate colonic transit and have antioxidant roles, but require further study in ageing colons.
5-HT(2) and 5-HT(4) mechanisms are implicated in enteric neuron development, maintenance, and survival.

Conclusions:

Understanding enteric neurodegeneration is key to developing effective treatments.
Neurotrophins show potential for medium-term relief of constipation and maintenance of enteric neurons.
Further research is essential to elucidate and potentially reverse enteric neurodegeneration for improved gastrointestinal health in ageing populations.