PUBLICATION

Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior

Authors
Yang, D., Lauridsen, H., Buels, K., Chi, L.H., La Du, J., Bruun, D., Olson, J.R., Tanguay, R.L., and Lein, P.
ID
ZDB-PUB-110316-27
Date
2011
Source
Toxicological sciences : an official journal of the Society of Toxicology   121(1): 146-59 (Journal)
Registered Authors
La Du, Jane K., Tanguay, Robyn L.
Keywords
axon outgrowth, chlorpyrifos, chlorpyrifos-oxon, developmental neurotoxicology, organophosphorus pesticides, zebrafish
MeSH Terms
  • Animals
  • Axons*
  • Chlorpyrifos/analogs & derivatives
  • Chromatography, High Pressure Liquid
  • Immunohistochemistry
  • Motor Activity/drug effects*
  • Swimming
  • Zebrafish/growth & development*
  • Zebrafish/physiology
PubMed
21346248 Full text @ Toxicol. Sci.
CTD
21346248
Abstract
Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO) or the excreted metabolite trichloro-2-pyridinol (TCPy) alter spatiotemporal patterns of axonal growth in vivo. Static waterborne exposure to CPFO, but not CPF or TCPy, at concentrations ≥ 0.03 μM from 24 to 72 hours post-fertilization significantly inhibited acetylcholinesterase, and high performance liquid chromatography detected significantly more TCPy in zebrafish exposed to 0.1 μM CPFO versus 1.0 μM CPF. These data suggest that zebrafish lack the metabolic enzymes to activate CPF during these early developmental stages. Consistent with this, CPFO, but not CPF, significantly inhibited axonal growth of sensory neurons, primary motoneurons and secondary motoneurons at concentrations ≥ 0.1 μM. Secondary motoneurons were the most sensitive to axonal growth inhibition by CPFO, which was observed at concentrations that did not cause mortality, gross developmental defects or aberrant somatic muscle differentiation. CPFO effects on axonal growth correlated with adverse effects on touch-induced swimming behavior, suggesting the functional relevance of these structural changes. These data suggest that altered patterns of neuronal connectivity contribute to the developmental neurotoxicity of CPF, and demonstrate the relevance of zebrafish as a model for studying OP developmental neurotoxicity.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping