Differing effects of NT-3 and GDNF on dissociated enteric ganglion cells exposed to hydrogen peroxide in vitro

Kris Korsak,Ayona T Silva,M Jill Saffrey

doi:10.1016/j.neulet.2012.04.036

Kris Korsak, Ayona T Silva + Show 1 more

Open Access

https://doi.org/10.1016/j.neulet.2012.04.036

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Journal: Neuroscience letters	Publication Date: Apr 22, 2012
Citations: 14	License type: cc-by

Affiliation: Universidade Aberta

Abstract

Oxidative stress is widely recognized to contribute to neuronal death during various pathological conditions and ageing. In the enteric nervous system (ENS), reactive oxygen species have been implicated in the mechanism of age-associated neuronal loss. The neurotrophic factors, neurotrophin 3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF), are important in the development of enteric neurons and continue to be expressed in the gut throughout life. It has therefore been suggested that they may have a neuroprotective role in the ENS. We investigated the potential of NT-3 and GDNF to prevent the death of enteric ganglion cells in dissociated cell culture after exposure to hydrogen peroxide (H2O2). H2O2 treatment resulted in a dose-dependent death of enteric neurons and glial cells, as demonstrated by MTS assay, bis-benzimide and propidium iodide staining and immunolabelling. Cultures treated with NT-3 prior to exposure showed reduced cell death compared to untreated control or GDNF-treated cultures. GDNF treatment did not affect neuronal survival in H2O2-treated cultures. These results suggest that NT-3 is able to enhance the survival of enteric ganglion cells exposed to oxidative stress.

Highlights

The neurons of the enteric nervous system (ENS), located in the wall of the digestive tract, regulate intestinal functions, such as motility and secretion [4,6,13]
Glial cell numbers were affected by glial cell line-derived neurotrophic factor (GDNF) in a manner similar to neurons, whereas glial cell numbers in neurotrophin 3 (NT-3)-treated cultures were not different than those found in controls
In this study, we investigated the effects of NT-3 and GDNF on cultured enteric ganglion cells exposed to H2O2

Summary

Introduction

The neurons of the enteric nervous system (ENS), located in the wall of the digestive tract, regulate intestinal functions, such as motility and secretion [4,6,13]. It has been suggested that increased survival of myenteric neurons in calorically-restricted animals might be due to the actions of neurotrophic factors present in the gut [37]. Two such factors, which continue to be expressed in the adult gut are neurotrophin 3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF)[5,32]. Treatment of segments of intestinal smooth muscle (muscularis externa, in which myenteric ganglia are embedded) from calorically-restricted rats with NT-3 and GDNF reduced neuronal ROS levels and enhanced resistance to menadione-induced apoptosis [37]

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