John Wiley & Sons, Ltd.

The developmental neurotoxicity of PBDEs: Effect of DE‐71 on dopamine in zebrafish larvae

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The potential neurotoxicity of polybrominated diphenyl ethers (PBDEs) is still a great concern. In the present study, we investigated whether exposure to PBDEs could affect the neurotransmitter system and cause developmental neurotoxicity in zebrafish. Two hours post fertilization (hpf) zebrafish embryos were exposed to different concentrations of the PBDE mixture DE‐71 (0‐100 µg/L). The larvae were harvested at 120 hpf and the impact on dopaminergic signaling was investigated. The results revealed significant reductions of whole‐body dopamine (DA) content and its metabolite, dihydroxyphenylacetic acid (DOPAC) content in DE‐71‐exposed larvae. The transcription of genes involved in the development of dopaminergic neurons (e.g. manf, bdnf, and nr4a2b) was significantly down‐regulated upon exposure to DE‐71. DE‐71 also resulted in a significant decrease of tyrosine hydroxylase (TH) and dopamine transporter protein levels in dopaminergic neurons. The expression level of TH in forebrain neurons was assessed by whole‐mount immunofluorescence, and the results further demonstrated that the TH protein expression level was reduced in dopaminergic neurons. In addition to these molecular changes, we also observed reduced locomotor activity in DE‐71‐exposed larvae. Taken together, the present study demonstrates that acute exposure to PBDEs can affect dopaminergic signaling through disrupting the synthesis and transportation of dopamine in zebrafish, thereby disrupting normal neurodevelopment. In accord with its experimental findings, this study extends our knowledge of the mechanisms governing PBDE‐induced developmental neurotoxicity. This article is protected by copyright. All rights reserved

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