title: Potentiation of Methylmercury-Induced Death in Rat Cerebellar Granular Neurons Occurs by Further Decrease of Total Intracellular GSH with BDNF via TrkB in Vitro.
abstract: Brain-derived neurotrophic factor (BDNF) is a principal factor for neurogenesis, neurodevelopment and neural survival through a BDNF receptor, tropomyosin-related kinase (Trk) B, while BDNF can also cause a decrease in the intracellular glutathione (GSH) level. We investigated the exacerbation of methylmercury-induced death of rat cerebellar granular neurons (CGNs) by BDNF in vitro. Since methylmercury can decrease intracellular GSH levels, we hypothesized that a further decrease of the intracellular GSH level is involved in the process of the exacerbation of neuronal cell death. In the present study, we established that in CGN culture, a decrease of the intracellular GSH level was further potentiated with BDNF in the process of the methylmercury-induced neuronal death and also in GSH reducer-induced neuronal death. BDNF treatment promoted the decrease in GSH levels induced by methylmercury and also by L-buthionine sulfoximine (BSO) and diethyl maleate (DEM). The promoting effect of BDNF was observed in a TrkB-vector transformant of the rat neuroblastoma B35 cell line but not in the mock-vector transformant. These results indicate that the exacerbating effect of BDNF on methylmercury-induced neuronal death in cultures of CGNs includes a further decrease of intracellular GSH levels, for which TrkB is essential.
authors.affiliation: Laboratory of Anatomy II, Department of Veterinary Medicine, School of Veterinary Medicine, Azabu University.
authors.forename: Motoharu
authors.initials: M
authors.lastname: Sakaue
authors.forename: Takehiro
authors.initials: T
authors.lastname: Maki
authors.forename: Takuya
authors.initials: T
authors.lastname: Kaneko
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hemmi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sekiguchi
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Horio
authors.forename: Erina
authors.initials: E
authors.lastname: Kadowaki
authors.forename: Aisa
authors.initials: A
authors.lastname: Ozawa
authors.forename: Masako
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008767:Methylmercury Compounds; D020813:Receptor, trkB; D005978:Glutathione