6-OH-BDE-47 exposure-induced Parkinson's disease pathology in Sprague Dawley rat

Fenfen Ji, Zhou Zhu, Mengtao Zhang, Huan Zhang, Lin Zhu, Xiaodong Cai, Wenlan Liu, Juxian Song, Min LI*, Zongwei CAI

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

6-Hydroxy-BDE-47 (6-OH-BDE-47) is an important in vivo metabolite derived from 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), a ubiquitous environmental pollutant. The chemical has been widely detected in environmental and biological samples. However, as a potential neurotoxin, whether 6-OH-BDE-47 could promote the development of typical neurodegenerative diseases such as Parkinson's disease (PD) is still unknown. Here, we tested the potential PD-related neurotoxic effect of 6-OH-BDE-47 in rat. The chemical with levels of 0.1, 1 and 10 µg was stereotaxically injected into the right midbrain regions of rat where contain abundant dopaminergic neurons. The resulting deteriorated motor function and decreased levels of striatal dopamine and nigrostriatal tyrosine hydroxylase indicate the dopaminergic neuron loss after the injection. Proteomics study revealed that protein degradation pathways were affected. Western blot analysis confirmed that 6-OH-BDE-47 could inhibit ubiquitination and autophagy, resulting in the increased formation of α-synuclein (α-syn) aggregate, an important pathological hallmark of PD. Overall, our study demonstrated that the 6-OH-BDE-47 administration could induce motor defect by impairing dopaminergic system and promote α-syn aggregation by inhibiting ubiquitination and autophagy, suggesting that the occurrence of 6-OH-BDE-47 in brain could be a risk for developing PD.

Original languageEnglish
Article number135184
JournalScience of the Total Environment
Volume711
DOIs
Publication statusPublished - 1 Apr 2020

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

User-Defined Keywords

  • 6-OH-BDE-47
  • autophagy
  • Parkinson's disease
  • ubiquitination
  • α-synuclein

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