Resveratrol promotes neurotrophic factor release from astroglia

Neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) are considered to contribute to the development, maintenance and survival of neurons, glia and oligodendrocytes. Astroglia are a major source of various neurotrophic factors. Thus, enhancement of astroglia-mediated neurotrophic factor release might hold promising potential for neurological diseases. Resveratrol, a natural non-flavonoid polyphenol found in grapes and red wine, has been recognized to be beneficial for health. Here, rat primary astroglia-enriched cultures were used to investigate the effects of resveratrol-mediated neurotrophic factor release and the related mechanisms. The cultures were treated with 25-100 mu mmol/L resveratrol for 12-48 h. Results showed resveratrol increased BDNF and GDNF production in the culture medium. In addition, the production of BDNF in the supernatant of cultures was increased five-fold over control cultures 24 h after resveratrol treatment and then remained high 36 h later. Meanwhile, the production of GDNF was initially increased by up to four-fold 24 h after resveratrol treatment and continued to increase to six-fold at 36 h and remained at a high level till 48 h. Western blot analysis of BDNF and GDNF protein in astroglia at different time points after resveratrol treatment indicated similar increases. Furthermore, resveratrol significantly induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP responsive element-binding protein (CREB) in astroglia. Overall, resveratrol is effective in promoting astroglia-derived neurotrophic factor release, and this effect is mediated, at least in part, by the activation of ERK1/2 and CREB.