The developmental neurotoxicity of polybrominated diphenyl ethers: Effect of DE-71 on dopamine in zebrafish larvae.

Abstract

The potential neurotoxicity of polybrominated diphenyl ethers (PBDEs) is still a great concern. In the present study, the authors investigated whether exposure to PBDEs could affect the neurotransmitter system and cause developmental neurotoxicity in zebrafish. Zebrafish embryos (2 h postfertilization) were exposed to different concentrations of the PBDE mixture DE-71 (0-100 μg/L). The larvae were harvested at 120 h postfertilization, and the impact on dopaminergic signaling was investigated. The results revealed significant reductions in content of whole-body dopamine and its metabolite, dihydroxyphenylacetic acid, in DE-71-exposed larvae. The transcription of genes involved in the development of dopaminergic neurons (e.g., manf, bdnf, and nr4a2b) was significantly downregulated upon exposure to DE-71. Also, DE-71 resulted in a significant decrease of tyrosine hydroxylase and dopamine transporter protein levels in dopaminergic neurons. The expression level of tyrosine hydroxylase in forebrain neurons was assessed by whole-mount immunofluorescence, and the results further demonstrated that the tyrosine hydroxylase protein expression level was reduced in dopaminergic neurons. In addition to these molecular changes, the authors observed reduced locomotor activity in DE-71-exposed larvae. Taken together, the results of the present study demonstrate that acute exposure to PBDEs can affect dopaminergic signaling by disrupting the synthesis and transportation of dopamine in zebrafish, thereby disrupting normal neurodevelopment. In accord with its experimental findings, the present study extends knowledge of the mechanisms governing PBDE-induced developmental neurotoxicity.