PUBLICATION
Tris (1-chloro-2-propyl) phosphate exposure to zebrafish causes neurodevelopmental toxicity and abnormal locomotor behavior
- Authors
- Xia, M., Wang, X., Xu, J., Qian, Q., Gao, M., Wang, H.
- ID
- ZDB-PUB-201208-5
- Date
- 2020
- Source
- The Science of the total environment 758: 143694 (Journal)
- Registered Authors
- Keywords
- Abnormal locomotor behavior, Gene expression change, Neurotoxicity, Tris (1-chloro-2-propyl) phosphate, Zebrafish
- MeSH Terms
-
- Animals
- Flame Retardants*/toxicity
- Organophosphates/toxicity
- Organophosphorus Compounds
- Phosphates
- Zebrafish*
- PubMed
- 33267995 Full text @ Sci. Total Environ.
Citation
Xia, M., Wang, X., Xu, J., Qian, Q., Gao, M., Wang, H. (2020) Tris (1-chloro-2-propyl) phosphate exposure to zebrafish causes neurodevelopmental toxicity and abnormal locomotor behavior. The Science of the total environment. 758:143694.
Abstract
The organophosphate flame retardant, tris (1-chloro-2-propyl) phosphate (TCPP), is ubiquitous in environmental matrices; however, there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of TCPP exposure on zebrafish neurodevelopment and swimming behavior to elucidate the underlying molecular mechanisms of neurotoxicity. Under TCPP gradient concentration exposure, the hatching rates were declined by up to 33.3% in 72 hpf, and the malformation rates increased from 15% to 50%. Meanwhile, TCPP led to abnormal behaviors including decreased locomotive activity in the dark and slow/insensitive responses to sound and light stimulation of larvae. TCPP caused excessive apoptosis and ROS accumulation in early embryonic development, with hair cell defects and structural deformity of neuromast. Abnormal expression of neurodevelopment (pax6a, nova1, sox11b, syn2a, foxo3a and robo2) and apoptosis-related genes (baxa, bcl2a and casp8) revealed molecular mechanisms regarding abnormal behavioral and phenotypic symptoms. Chronic TCPP exposure led to anxiety-like behavior and excessive panic, lower capacity for discrimination and risk avoidance, and conditioned place preference in adults. Social interaction tests demonstrated that long-term TCPP stress resulted in unsociable, eccentric, lonely and silent behaviors in adults. Zebrafish memory and cognitive function were severely reduced as concluded from T-maze tests. Potential mechanisms triggering behavioral abnormality were attributed to histopathological injury of diencephalon, abnormal changes in nerve-related genes at transcription and expression levels, and inhibited activity of AChE by TCPP stress. These findings provide an important reference for risk assessment and early warning to TCPP exposure, and offer insights for prevention/mitigation of pollutant-induced nervous system diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping