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Sci Total Environ. 2020 Apr 1;711:135184. doi: 10.1016/j.scitotenv.2019.135184. Epub 2019 Nov 23.

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

Author information

1
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China.
2
Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
3
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China; School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen, China.
4
Department of Functional Neurology & Neurosurgery, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
5
The Central Laboratory and Shenzhen Key Laboratory of Neurosurgery, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
6
Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
7
Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address: limin@hkbu.edu.hk.
8
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address: zwcai@hkbu.edu.hk.

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.

KEYWORDS:

6-OH-BDE-47; Parkinson’s disease; autophagy; ubiquitination; α-synuclein

Conflict of interest statement

Declaration of Competing Interest There are no conflicts of interest to declare.

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