Fenpropathrin induces degeneration of dopaminergic neurons via disruption of the mitochondrial quality control system.

Cell Death Discovery
Zhigang JiaoShaogang Qu

Abstract

The synthetic pyrethroid derivative, fenpropathrin, is a widely used insecticide. However, a variety of toxic effects in mammals have been reported. In particular, fenpropathrin induces degeneration of dopaminergic neurons and parkinsonism. However, the mechanism of fenpropathrin-induced parkinsonism has remained unknown. In the present study, we investigated the toxic effects and underlying mechanisms of fenpropathrin on perturbing the dopaminergic system both in vivo and in vitro. We found that fenpropathrin induced cellular death of dopaminergic neurons in vivo. Furthermore, fenpropathrin increased the generation of reactive oxygen species, disrupted both mitochondrial function and dynamic networks, impaired synaptic communication, and promoted mitophagy in vitro. In mice, fenpropathrin was administered into the striatum via stereotaxic (ST) injections. ST-injected mice exhibited poor locomotor function at 24 weeks after the first ST injection and the number of tyrosine hydroxylase (TH)-positive cells and level of TH protein in the substantia nigra pars compacta were significantly decreased, as compared to these parameters in vehicle-treated mice. Taken together, our results demonstrate that exposure to fenpropathrin induces...Continue Reading

References

Feb 1, 1977·Japanese Journal of Pharmacology·H KuribaraS Tadokoro
Oct 3, 2002·Nature Medicine·Laura Bonetta
Feb 15, 2007·Journal of Cell Science·Giovanni BenardRodrigue Rossignol
Apr 3, 2007·Nature Protocols·Vernice Jackson-Lewis, Serge Przedborski
Aug 28, 2007·The Journal of Comparative Neurology·Gilmor I KeshetHelen M Blau
Dec 21, 2007·Lancet Neurology·Anthony H V Schapira
Oct 1, 2010·The Journal of Pharmacology and Experimental Therapeutics·Zhengyu CaoThomas F Murray
Dec 15, 2010·Brain Research Reviews·P Hemachandra ReddyPeizhong Mao
Jan 6, 2012·Nature Reviews. Neuroscience·Zu-Hang Sheng, Qian Cai
May 9, 2012·The Journal of Cell Biology·Yusuke KageyamaHiromi Sesaki
Jun 7, 2012·Neurobiology of Disease·Victor S Van Laar, Sarah B Berman
Sep 1, 2012·Science·Richard J Youle, Alexander M van der Bliek
Jul 13, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Shaheen ChikteGary Warnes
Sep 21, 2013·Annual Review of Pharmacology and Toxicology·Samuel M Goldman
Oct 12, 2013·Current Biology : CB·Huyen T Bui, Janet M Shaw
Oct 24, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Amandine BerthetKen Nakamura
Nov 6, 2014·Nature Communications·Phillip M RappoldKim Tieu
Jan 13, 2015·Molecular Neurobiology·Jing XiongTao Wang
Mar 12, 2015·Trends in Biochemical Sciences·Brent J RyanRichard Wade-Martins
Oct 27, 2015·Cell·Gerald S Shadel, Tamas L Horvath
Nov 26, 2015·The Journal of Cell Biology·Hsiuchen ChenDavid C Chan
Feb 29, 2016·Pharmacological Reports : PR·Barbara Nieradko-Iwanicka, Andrzej Borzęcki
Oct 12, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ilhem RjeibiNajla Hfaiedh
Jan 31, 2017·Nature Communications·Babette C HammerlingÅsa B Gustafsson
Jan 13, 2018·BMC Biology·Shiori Sekine, Richard J Youle
Feb 21, 2018·Current Biology : CB·Sarah PicklesRichard J Youle
May 5, 2018·Human Molecular Genetics·Kyle DentonXue-Jun Li

❮ Previous
Next ❯

Citations

Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ammar BaderMajed Halwani

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
confocal microscopy
ELISA
transmission electron microscopy
fluorescence
Assay
Protein Assay
electrophoresis

Software Mentioned

Pro Plus
SPSS
Image
Maze
ImageJ
Leica LASX
Any

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.