Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury

• Cultured astrocytes have more tolerance to MeHg toxicity than neuronal cells.
• Astrocytes synthesize and release NGF and BDNF in response to MeHg.
• NGF and BDNF signaling attenuates MeHg toxicity in neuronal cells.
• NGF and BDNF from astrocytes could confer MeHg tolerance on neuronal cells.

The protective roles of astrocytes in neurotoxicity induced by environmental chemicals, such as methylmercury (MeHg), are largely unknown. We found that conditioned medium of MeHg-treated astrocytes (MCM) attenuated neuronal cell death induced by MeHg, suggesting that astrocytes-released factors can protect neuronal cells. The increased expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) was observed in MeHg-treated astrocytes. NGF and BDNF were detected in culture media as homodimers, which are able to bind specific tyrosine kinase receptors, tropomyosin related kinase (Trk) A and TrkB, respectively. The TrkA antagonist and TrkB antagonist abolished the protective effects of MCM in neuronal cell death induced by MeHg. Taken together, astrocytes synthesize and release NGF and BDNF in response to MeHg to protect neurons from MeHg toxicity. This study is considered to show a novel defense mechanism against MeHg-induced neurotoxicity.