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Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

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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. Dcreased 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.

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Abbreviations

Fen:

Fenpropathrin

PD:

Parkinson’s disease

i.p:

Intraperitoneal injection

ST:

Stereotaxical injection

DAT:

Dopamine transporter

VMAT2:

Vesicular monoamine transporter 2

DA:

Dopamine

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Acknowledgments

This work was supported by grants 30870866, 81071021, and 31171211 from the National Natural Science Foundation of China (to TW); grant 81200983 from the National Natural Science Foundation of China (to NX); grant 81100958 from the National Natural Science Foundation of China (to ZTZ); grant 81301082 from the National Natural Science Foundation of China (to JSH); grant 2012B09 from China Medical Foundation (to NX); and grant 0203201343 from Hubei Molecular Imaging Key Laboratory (to NX). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of Interest

There are no actual or potential conflicts of interest.

Authors’ Contributions

JX, XZ, JH, CC, ZC, LL, JY, ZZ, NX, and TW contributed to the conception and design. JX, XZ, JH, and CC took care of the cell culture studies. JX, XZ, ZC, LL, and JY took care of the animal studies. JX, XZ, JH, CC, ZC, and NX analyzed and interoperated the data. JX, XZ, JH, NX, and TW coordinated all the experiments and helped to draft the manuscript. All authors read, revised, and approved the final manuscript.

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    Authors and Affiliations

    1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China

      Jing Xiong, Xiaowei Zhang, Jinsha Huang, Chunnuan Chen, Zhenzhen Chen, Ling Liu, Guoxin Zhang, Jiaolong Yang, Nian Xiong & Tao Wang

    2. Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China

      Jing Xiong, Zhentao Zhang & Zhaohui Zhang

    3. Department of Neurology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China

      Chunnuan Chen

    4. Department of Psychiatry, Harvard Medical School; Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, 02478, USA

      Zhicheng Lin

    5. Harvard NeuroDiscovery Center, Boston, MA, 02114, USA

      Zhicheng Lin

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    1. Jing Xiong
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    Correspondence to Nian Xiong or Tao Wang.

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    Jing Xiong, Xiaowei Zhang, and Jinsha Huang equally contributed to the work.

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    Xiong, J., Zhang, X., Huang, J. et al. Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration. Mol Neurobiol 53, 995–1008 (2016). https://doi.org/10.1007/s12035-014-9057-2

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