2. Academic Validation
  3. Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

  • Mol Neurobiol. 2016 Mar;53(2):995-1008. doi: 10.1007/s12035-014-9057-2.
Jing Xiong 1 2,  Xiaowei Zhang 1,  Jinsha Huang 1,  Chunnuan Chen 1 3,  Zhenzhen Chen 1,  Ling Liu 1,  Guoxin Zhang 1,  Jiaolong Yang 1,  Zhentao Zhang 2,  Zhaohui Zhang 2,  Zhicheng Lin 4 5,  Nian Xiong 6,  Tao Wang 7
Affiliations

Affiliations

  • 1 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
  • 2 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
  • 3 Department of Neurology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
  • 4 Department of Psychiatry, Harvard Medical School; Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, 02478, USA.
  • 5 Harvard NeuroDiscovery Center, Boston, MA, 02114, USA.
  • 6 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. nianxiongtjmu@gmail.com.
  • 7 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. wangtaowh@hust.edu.cn.
PMID: 25575680 DOI: 10.1007/s12035-014-9057-2
Abstract

Fenpropathrin is one of the widely used pyrethroids in agriculture and household and also reported to have neurotoxic effects in rodent models. In our Parkinson's disease (PD) clinic, there was a unique patient with a history of daily exposure to fenpropathrin for 6 months prior to developing Parkinsonian symptoms progressively. Since whether fenpropathrin is related to any dopaminergic degeneration was unknown, we aimed in this study to evaluate the neurotoxic effects of fenpropathrin on the dopaminergic system and associated mechanisms in vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death, Reactive Oxygen Species generation, Lewy body-associated proteins aggregation, and Lewy body-like intracytoplasmic inclusions formation. In rodent Animals, two different injections of fenpropathrin were used for administrations, intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of pokes 60 days after first i.p injection, while the rats in ST group showed a significant upregulation of apomorphine-evoked rotations 60 days after first injection. Decreased tyrosine hydroxylase (TH) and vesicular Monoamine Transporter 2 (VMAT2) immunoreactivity, while increased Dopamine Transporter (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days after the last exposure to fenpropathrin. However, the number of TH-positive cells in the substantia nigra was more reduced 120 days after the first i.p injection than those of 60 days. Our data demonstrated that exposure to fenpropathrin could mimic the pathologic and pathogenetic features of PD especially in late onset cases. These results imply fenpropathrin as a DA neurotoxin and a possible environmental risk factor for PD.

Keywords

Dopamine; Dopamine transporter; Fenpropathrin; Parkinson’s disease; Tyrosine hydroxylase; Vesicular monoamine transporter 2.

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