title: Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration.
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.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.|Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
authors.forename: Jinsha
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.|Department of Neurology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China.
authors.forename: Jiaolong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Harvard Medical School; Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, 02478, USA.|Harvard NeuroDiscovery Center, Boston, MA, 02114, USA.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. nianxiongtjmu@gmail.com.
authors.forename: Nian
authors.initials: N
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D016631:Lewy Bodies / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010575:Pesticides / Q000633:toxicity*; D066329:Protein Aggregates / Q000187:drug effects; D011722:Pyrethrins / Q000633:toxicity*; D016601:RNA-Binding Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C118585:P62 protein, human; D010575:Pesticides; D066329:Protein Aggregates; D011722:Pyrethrins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; C493454:Slc18a2 protein, rat; D025801:Ubiquitin; D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; C044267:fenpropathrin; D020782:Matrix Metalloproteinases; D004298:Dopamine
keywords: Dopamine; Dopamine transporter; Fenpropathrin; Parkinson’s disease; Tyrosine hydroxylase; Vesicular monoamine transporter 2