Changes in the enteric nervous system and surrounding cells during ageing

The enteric nervous system continues to undergo changes throughout life. Changes in both enteric neurons and glial cells in old age have been reported, but our understanding both of the effects of described changes on gastrointestinal function and the causes of age-related changes are poorly understood. We are analysing changes in the enteric nervous system and surrounding cells in the intestine of the C57/Bl6 mouse during ageing, using a multidisciplinary approach. We are focusing on the large intestine and terminal bowel; regions that are implicated in changes that may contribute to the increased incidence of constipation and incontinence in the elderly population. The progression of age-associated changes is studied by analysing tissues from animals at 3, 12, 18 and 24 months of age. Changes in the numbers and phenotypic properties of neurons and nerve fibre density and also changes in Interstitial cells, fibroblast-like cells and enteroendocrine cells are being studied in both tissue sections and whole mount preparations by immunohistochemistry, confocal and electron microscopy. Physiological and pharmacological analysis of tissues is also performed and the combined data from all these types of approach allows us to understand more fully how ageing affects neural and non-neural regulation of gut functions. Our data show that changes in the responses of the distal colon, rectum and internal anal sphincter in vitro occur during ageing, and that these changes are complex, involve several different signalling systems and do not simply relate to changes in cell number. In addition, we are investigating the mechanisms that cause age-related changes in both neurons and non-neural cells in the intestine, using a combination of markers and imaging techniques. Our preliminary data indicate that the different cell types involved in the regulation of gastrointestinal motility may be differentially affected during ageing. A detailed understanding of ageing of the ENS and surrounding cells will provide valuable information to increase our understanding of age-associated gastrointestinal dysfunction

Investigating the effect of photodynamic therapy on nerves using tissue engineered culture models

Introduction: Photodynamic therapy (PDT) shows potential as an effective treatment for prostate cancer. Clinical observations indicate that this approach causes fewer nerve damage related side-effects than conventional treatments. The aim here is to investigate the effect of PDT on nerve tissue using engineered 3-dimensional cell culture models. Initial experiments focussed on establishing photosensitiser localisation in neurones and Schwann cells, then developing a model for simulating nerve PDT in culture

Aging of the nervous system

About the book: During the last 40 years, the study of the biological basis of aging has progressed tremendously, and it has now become an independent and respectable field of study and research. This volume on "Aging of Organs and Systems", is an attempt to bring understanding to both the aging process and the disease processes of old age. Bringing together contributions from an international team of authors, it will be of interest to graduates and postgraduates in the fields of medicine and nursing, researchers of different aspects of biogerontology and those in the pharmaceutical, cosmeceutical, nutriceutical and health-care industry

Role of neurotrophic factors (NTF) and extracellular matrix components (ECM) on VIP expression in the rat enteric nervous system (ENS)

We studied changes in vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expression by myenteric neurons during early postnatal development in parallel with maturation of the environment of myenteric neurons, specifically the expression of ECM components and NTF. Although these molecules are known to promote neuronal differentiation [Shetty & Turner, 1998: Sieber-Blum et al. 1981], very little is known about their role in the early postnatal ENS. Sprague-Dawley rats were killed by cervical dislocation. The ileal muscularis externa, including myenteric ganglia, was processed for semi-quantitative RT-PCR at postnatal days P1, P7 and P21 (internal standards: βIII tubulin and PGP9.5). VIP (Fig. 1), nNOS and NT-3 mRNA levels showed a consistent increase between P1 and P21. Although no changes in GDNF mRNA levels were observed, there was an increase in levels of mRNA of its co-receptor, GFRα-1, indicating that the responsiveness of myenteric neurons to GDNF might be enhanced at older ages. Immunofluorescent labelling of ileal cross sections revealed changes in the levels of laminin (peak at P7) and fibronectin (peak at P21). Next, we tested the effect of ECM and NTF on myenteric neurons in cultures of dissociated myenteric ganglia (P7/8) [Schafer et al. 1997]. Changes in cell numbers per unit area of coverslips were measured after double labelling for βIII tubulin and VIP. GDNF, but not NT-3 or BDNF (all at 1 ng/ml), enhanced survival of the overall neuronal population (35-67% increase, n=3 experiments, P<0.02, paired t-test) and the percentage of VIP positive neurons (39-59%, n=3, P<0.02). Elevation of VIP and nNOS mRNA levels after treatment with GDNF was confirmed by RT-PCR. The effect of GDNF on neuronal survival was maintained in the presence of laminin (26-58% increase, n=3, P<0.05) and fibronectin (34-55%, n=3, P<0.012), although neither factor alone influenced neuronal survival. Fibronectin (10-18% increase, n=3, P=0.10), but not laminin (19-81% increase, n=3, P<0.04), reduced the effect of GDNF on the proportion of VIP positive neurons. Our study suggests that GDNF regulates VIP and nNOS expression by myenteric neurons. Fibronectin was found to influence the effect of GDNF on VIP phenotype. Together with the observed changes in the environment of myenteric neurons in the early postnatal gut, our results indicate that both NTF and ECM components are likely to contribute to postnatal development of the ENS