Chlorpyrifos-oxon disrupts zebrafish axonal growth and motor behavior.

TitleChlorpyrifos-oxon disrupts zebrafish axonal growth and motor behavior.
Publication TypeJournal Article
Year of Publication2011
AuthorsYang, D, Lauridsen, H, Buels, K, Chi, L-H, La Du, J, Bruun, DA, Olson, JR, Tanguay, RL, Lein, PJ
JournalToxicol Sci
Date Published2011 May
KeywordsAnimals, Axons, Chlorpyrifos, Chromatography, High Pressure Liquid, Immunohistochemistry, Motor Activity, Swimming, Zebrafish

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-h 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.

Alternate JournalToxicol. Sci.
PubMed ID21346248
PubMed Central IDPMC3080187
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R01 ES016308 / ES / NIEHS NIH HHS / United States
ES00210 / ES / NIEHS NIH HHS / United States
ES016308 / ES / NIEHS NIH HHS / United States