PUBLICATION
Zebrafish Provide a Sensitive Model of Persisting Neurobehavioral Effects of Developmental Chlorpyrifos Exposure: Comparison with Nicotine and Pilocarpine Effects and Relationship to Dopamine Deficits
- Authors
- Eddins, D., Cerutti, D., Williams, P., Linney, E., and Levin, E.D.
- ID
- ZDB-PUB-090310-20
- Date
- 2010
- Source
- Neurotoxicology and teratology 32(1): 99-108 (Journal)
- Registered Authors
- Linney, Elwood
- Keywords
- Zebrafish, Chlorpyrifos, Nicotine, Pilocarpine, Startle Response, Development
- MeSH Terms
-
- Animals
- Brain/drug effects
- Brain/metabolism
- Chlorpyrifos/toxicity*
- Dopamine/metabolism
- Female
- Habituation, Psychophysiologic/drug effects
- Insecticides/toxicity
- Larva/drug effects*
- Larva/metabolism
- Maternal Exposure
- Models, Animal*
- Muscarinic Agonists/toxicity*
- Nicotine/toxicity*
- Nicotinic Agonists/toxicity
- Pilocarpine/toxicity*
- Reflex, Startle/drug effects*
- Serotonin/metabolism
- Time Factors
- Toxicity Tests/methods
- Zebrafish/metabolism*
- PubMed
- 19268529 Full text @ Neurotoxicol. Teratol.
Citation
Eddins, D., Cerutti, D., Williams, P., Linney, E., and Levin, E.D. (2010) Zebrafish Provide a Sensitive Model of Persisting Neurobehavioral Effects of Developmental Chlorpyrifos Exposure: Comparison with Nicotine and Pilocarpine Effects and Relationship to Dopamine Deficits. Neurotoxicology and teratology. 32(1):99-108.
Abstract
Chlorpyrifos (CPF) an organophosphate pesticide causes persisting behavioral dysfunction in rat models when exposure is during early development. In earlier work zebrafish were used as a complementary model to study mechanisms of CPF-induced neurotoxicity induced during early development. We found that developmental (first five days after fertilization) chlorpyrifos exposure significantly impaired learning in zebrafish. However, this testing was time and labor intensive. In the current study we tested the hypothesis that persisting effects of developmental chlorpyrifos could be detected with a brief automated assessment of startle response and that this behavioral index could be used to help determine the neurobehavioral mechanisms for persisting CPF effects. The swimming activity of adult zebrafish was assessed by a computerized video-tracking device after a sudden tap to the test arena. Ten consecutive trials (1/min) were run to determine startle response and its habituation. Additionally, habituation recovery trials were run at 8, 32 and 128 minutes after the end of the initial trial set. CPF-exposed fish showed a significantly (p<0.025) greater overall startle response during the 10-trial session compared to controls (Group sizes: Control N=40, CPF N=24). During the initial recovery period (8 min) CPF-exposed fish showed a significantly (p<0.01) greater startle response compared to controls. To elucidate the contributions of nicotinic and muscarinic acetylcholine receptors to developmental CPF-mediated effects, the effects of developmental nicotine and pilocarpine exposure throughout the first five days after fertilization were determined. Developmental nicotine and pilocarpine exposure significantly increased startle response, though nicotine (Group sizes: Control N=32, 15 mM N=12, 25 mM N=20) was much more potent than pilocarpine (Group sizes: Control N=20, 100 muM N=16, 1,000 muM N=12). Neither was as potent as CPF for developmental exposure increasing startle response in adulthood. Lastly, developmental CPF exposure decreased dopamine and serotonin levels and increased transmitter turnover in developing zebrafish larvae (N=4 batches of 50 embryos/treatment). Only the decline in dopamine concentrations persisted into adulthood (Group Sizes Control N=14, CPF N=13). This study shows that a quick automated test of startle can detect persisting neurobehavioral impairments caused by developmental exposure to CPF. This may be helpful in screening for persisting neurobehavioral defects from a variety of toxicants.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping