title: The neurotoxicity of DE-71: effects on neural development and impairment of serotonergic signaling in zebrafish larvae.
abstract: The underlying mechanism of polybrominated diphenyl ether (PBDE)-induced neurotoxicity is still a major concern due to its ubiquitous nature and persistence. Here, zebrafish embryos (2 h postfertilization, hpf) were exposed to different concentrations of the commercial PBDE mixture DE-71 (0-100 µg l-1) until 120 hpf, and the impact on neural development and serotonergic system was investigated. The in vivo results revealed significantly reduced transcription of genes involved in neurogenesis (fgf8, shha, wnt1), and contents of proteins in neuronal morphogenesis (myelin basic protein, synapsin IIa), suggesting an impairment of neural development in zebrafish embryos. Further results demonstrated a reduction of 5-hydroxytryptamine neuron and a dose-dependent decrease of whole-body serotonin levels, as well as the transcription of genes involved in serotonergic synthesis (tph1, tph2, trhr) and neurotransmission (serta/b, htr1aa/b). In addition, we predicted possible targets of PBDEs by molecular docking, and the results indicated that PBDE congeners showed high binding affinities with fibroblast growth factor 8 other than SHH and HTR1B. Taken together, this study demonstrated that PBDE exposure during embryogenesis could damage neural development and cause impairment of the serotonergic system as secondary effects in the zebrafish larvae. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.|University of Chinese Academy of Sciences, Beijing, 100039, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China. lhyang@ihb.ac.cn.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Qiangwei
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007814:Larva; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects* / Q000235:genetics; D059326:Serotonergic Neurons / Q000187:drug effects*; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D012701:Serotonin; C086401:pentabromodiphenyl ether
keywords: PBDEs; molecular docking; neural development; serotonergic system; zebrafish larvae