title: Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury.
abstract: 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.
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takemoto
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan. Electronic address: ishiyasu@hiroshima-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Ishida
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D020932:Nerve Growth Factor / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000037:antagonists & inhibitors; D020813:Receptor, trkB / Q000037:antagonists & inhibitors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; C000606649:GW 441756; D007211:Indoles; D008767:Methylmercury Compounds; D010456:Peptides, Cyclic; C554840:cyclotraxin-B; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB
keywords: Astrocyte; Brain-derived neurotrophic factor; Methylmercury; Nerve growth factor; Neurotoxicity