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.
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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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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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DOI: https://doi.org/10.1007/s12035-014-9057-2