Astrocyte-secreted GDNF and glutathione antioxidant system protect neurons against 6OHDA cytotoxicity

Neurobiology of Disease

Mossa Gardaneh¹  Marianna Sikorska²  Sandhya Gangaraju³  Rafal Iwasiow³  Roger Tremblay³  Kazutoshi Kiuchi³  Maria Ribecco-Lutkiewicz³  Jagdeep K. Sandhu³  Patricia Lanthier³ 

[1] Corresponding authors. Fax: [phone].;Department of Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, 501-1193, Gifu, Japan;Neurogenesis and Brain Repair Group, M54, Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Ottawa, Ontario, Canada K1A 0R6;

关键词: Neuroprotection;    Neuro-regeneration;    Neurotrophic factor;    Signal transduction;    Thiol antioxidant;    Coculture;   

DOI  :  

来源: DOAJ

【 摘 要 】

In recent years, GDNF has emerged as a protective and restorative agent in several models of neurodegeneration; however, the exact molecular mechanisms responsible for these effects are not yet fully understood. Here we examined the effects of astrocytes secreting GDNF on neurons subjected to 6OHDA toxicity using in vitro neuron-astroglia co-cultures. Astrocytes were transduced with lentiviral vectors carrying the GDNF gene under the control of either human glial fibrillary acidic protein or cytomegalovirus promoters. The overexpression of GDNF, regardless of the promoter employed, had no obvious adverse effects on astroglia and the engineered cells stably produced and secreted GDNF for extended periods of time (≥3 weeks). These astrocytes very effectively protected neurons against 6OHDA, in both mouse and human co-culture systems. The neuroprotective effects were mediated not only by GDNF, but also by the antioxidant GSH since its depletion reduced the level of GDNF protection. Furthermore, neurons and astrocytes expressed different components of GDNF signaling complex, suggesting that they might utilize separate pathways to mediate autocrine and paracrine effects of GDNF.

【 授权许可】

Unknown