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

Oxidative stress is widely recognized to contribute to neuronal death during various pathological conditions and aging. 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 neuoprotective role in the ENS. We investigated the potential of NT-3 and GDNF to prevent 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