Journal
CHEMOSPHERE
Volume 243, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2019.125336
Keywords
Fenvalerate; Autophagy; Parkinson-like symptom; p38 MAPK/mTOR signaling pathway; Zebrafish
Categories
Funding
- National Natural Science Foundation of China [81573194, 91743205, 81973091, 81903353]
- National 973 Program of China [2009CB941701]
- Top-notch Academic Programs Project of Jiangsu Higher Education Institutions of China [PPZY 2015A067]
- Project of Priority Academic Program Development of Jiangsu Higher Education Institutions of China [JX103318021]
Ask authors/readers for more resources
Fenvalerate (FEN), one of the most used synthetic pyrethroids, has the potential to interfere with human neural function. , Flowever, far too little attention was paid to the mechanism of FEN-induced neurotoxicity. Thus we exposed zebrafish to FEN from 4 to 120 h post fertilization (hpf), and analyzed the morphology and behavior of zebrafish. Our results showed that FEN decreased the survival rate of zebrafish, with increased malformation rates and abnormal behaviors. Furthermore, we found typical parkinson-like symptoms in FEN-exposed zebrafish with increases in parkinson's disease (PD), ubiquitin, and Lewy bodies-relevant genes. We also observed the loss of dopaminergic neurons in both FEN-exposed zebrafish and PC12 cells, which were all associated with PD-like symptoms. Besides, FEN activated autophagy by the enhanced expressions of p-mTOR, and LC3-II but the reduction of p62. Further, FEN initially activated p-p38 MAPK followed by p-mTOR, which triggered the transcription of genes responsible for autophagy process and prompted the Lewy bodies neuron generation leading to the PD-like symptoms. This process was inhibited by both 3-methyladenine (3-MA, an autophagy inhibitor) and SB203580 (a p38 MAPK selective inhibitor) in zebrafish and PC12 cells. These results suggest that FEN might cause parkinson-like symptom during zebrafish development through induction of autophagy and activation of p38 MAPK/mTOR signaling pathway. The study revealed the potential mechanism of FEN-induced neurotoxicity and should give new insights into a significant environmental risk factor of developing parkinson's disease. (C) 2019 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available