Affiliation:
1. Henan International Joint Laboratory of Aquatic Toxicology and Health Protection, College of Life Science, Henan Normal University, Xinxiang 453007, China
2. State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academic of Sciences, Wuhan 430072, China
3. College of Fisheries, Henan Normal University, Xinxiang 453007, China
Abstract
Trichlorfon is an organophosphorus pesticide widely used in aquaculture and has potential neurotoxicity, but the underlying mechanism remains unclear. In the present study, zebrafish embryos were exposed to trichlorfon at concentrations (0, 0.1, 2 and 5 mg/L) used in aquaculture from 2 to 144 h post fertilization. Trichlorfon exposure reduced the survival rate, hatching rate, heartbeat and body length and increased the malformation rate of zebrafish larvae. The locomotor activity of larvae was significantly reduced. The results of molecular docking revealed that trichlorfon could bind to acetylcholinesterase (AChE). Furthermore, trichlorfon significantly inhibited AChE activity, accompanied by decreased acetylcholine, dopamine and serotonin content in larvae. The transcription patterns of genes related to acetylcholine (e.g., ache, chrna7, chata, hact and vacht), dopamine (e.g., drd4a and drd4b) and serotonin systems (e.g., tph1, tph2, tphr, serta, sertb, htrlaa and htrlab) were consistent with the changes in acetylcholine, dopamine, serotonin content and AChE activity. The genes related to the central nervous system (CNS) (e.g., a1-tubulin, mbp, syn2a, shha and gap-43) were downregulated. Our results indicate that the developmental neurotoxicity of trichlorfon might be attributed to disorders of cholinergic, dopaminergic and serotonergic signaling and the development of the CNS.
Funder
National Natural Science Foundation of China
the Scientific and Technological Project of Henan Province
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis