PUBLICATION

The neurotoxicity of DE-71: effects on neural development and impairment of serotonergic signaling in zebrafish larvae

Authors
Wang, X., Yang, L., Wang, Q., Guo, Y., Li, N., Ma, M., Zhou, B.
ID
ZDB-PUB-160324-17
Date
2016
Source
Journal of applied toxicology : JAT   36(12): 1605-1613 (Journal)
Registered Authors
Keywords
PBDEs, molecular docking, neural development, serotonergic system, zebrafish larvae
MeSH Terms
  • Animals
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/metabolism
  • Environmental Pollutants/toxicity*
  • Halogenated Diphenyl Ethers/toxicity*
  • Larva
  • Motor Activity/drug effects
  • Neurogenesis/drug effects*
  • Neurogenesis/genetics
  • Serotonergic Neurons/drug effects*
  • Serotonin/genetics
  • Serotonin/metabolism*
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Transcription, Genetic/drug effects
  • Zebrafish/embryology*
  • Zebrafish/metabolism
PubMed
27001416 Full text @ J. Appl. Toxicol.
CTD
27001416
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping