Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biology, Cell Biology, Life Sciences & Biomedicine - Other Topics, enteric nervous system, neuronal death, neuroprotection, active caspase 3, SLOW-TRANSIT CONSTIPATION, ADULT TRANSGENIC MICE, NERVOUS-SYSTEM, MYENTERIC NEURONS, ASTROCYTES, EXPRESSION, SURVIVAL, ABLATION, DISEASE, NEUROPATHOLOGY, Animals, Calcium, Caspase 3, Cell Line, Tumor, Dopamine, Female, Gastrointestinal Tract, Gene Silencing, Glutathione, Hydrogen Peroxide, Nerve Tissue Proteins, Neuroglia, Neurons, Oxidants, Oxidation-Reduction, Oxidative Stress, Phosphopyruvate Hydratase, Pregnancy, RNA, Messenger, Rats, Rats, Sprague-Dawley, 0601 Biochemistry and Cell Biology, 0606 Physiology, 1116 Medical Physiology, 3101 Biochemistry and cell biology, 3208 Medical physiology

Abstract:

Enteric glial cells (EGCs) are essential in the control of gastrointestinal functions. Although lesions of EGCs are associated with neuronal degeneration in animal models, their direct neuroprotective role remains unknown. Therefore, the aims of this study were to demonstrate the direct neuroprotective effects of EGCs and to identify putative glial mediators involved. First, viral targeted ablation of EGCs in primary cultures of enteric nervous system increased neuronal death both under basal conditions and in the presence of oxidative stress (dopamine, hydrogen peroxide). Second, direct or indirect coculture experiments of EGC lines with primary cultures of enteric nervous system or neuroblastoma cell lines (SH-SY5Y) prevented neurotoxic effects induced by oxidative stress (increased membrane permeability, release of neuronal specific enolase, caspase-3 immunoreactivity, changes in [Ca(2+)]i response). Finally, combining pharmacological inhibition and mRNA silencing methods, we demonstrated that neuroprotective effects of EGCs were mediated in part by reduced glutathione but not by oxidized glutathione or by S-nitrosoglutathione. Our study identified the neuroprotective effects of EGCs via their release of reduced glutathione, extending their critical role in physiological contexts and in enteric neuropathies.-Abdo, H., Derkinderen, P., Gomes, P., Chevalier, J., Aubert, P., Masson, D., Galmiche, J.-P., Vanden Berghe, P., Neunlist, M., Lardeux, B. Enteric glial cells protect neurons from oxidative stress in part via reduced glutathione.