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

Ji, Fenfen1; Zhu, Zhou2; Zhang, Mengtao1,5; Zhang, Huan2; Zhu, Lin1; Cai, Xiaodong3; Liu, Wenlan4; Song, Juxian2,6; Li, Min2; Cai, Zongwei1

2020

10.1016/j.scitotenv.2019.135184

Science of the Total Environment   影响因子和分区

18791026

1879-1026

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.
© 2019 Elsevier B.V.

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

SCI ; EI

英语

其他

National Basic Research Program of China (973 Program)[2017YFC1600505] ; Hong Kong Baptist University[RC-IRMS/15-16/04]

Environmental Sciences & Ecology

Environmental Sciences

WOS:000509344700002

Elsevier B.V.

20195107882831

Amines ; Amino acids ; Cell death ; Electrophoresis ; Metabolites ; Molecular biology ; Neurons ; Rats

Medicine and Pharmacology:461.6 ; Biology:461.9 ; Electricity: Basic Concepts and Phenomena:701.1 ; Organic Compounds:804.1

ENVIRONMENT/ECOLOGY

Web of Science

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

Ji, Fenfen,Zhu, Zhou,Zhang, Mengtao,et al. 6-OH-BDE-47 exposure-induced Parkinson's disease pathology in Sprague Dawley rat[J]. Science of the Total Environment,2020,711.

Ji, Fenfen.,Zhu, Zhou.,Zhang, Mengtao.,Zhang, Huan.,Zhu, Lin.,...&Cai, Zongwei.(2020).6-OH-BDE-47 exposure-induced Parkinson's disease pathology in Sprague Dawley rat.Science of the Total Environment,711.

Ji, Fenfen,et al."6-OH-BDE-47 exposure-induced Parkinson's disease pathology in Sprague Dawley rat".Science of the Total Environment 711(2020).