PUBLICATION
The Developmental Neurotoxicity of Fipronil: Notochord Degeneration and Locomotor Defects in Zebrafish Embryos and Larvae
- Authors
- Stehr, C.M., Linbo, T.L., Incardona, J.P., and Scholz, N.L.
- ID
- ZDB-PUB-060419-1
- Date
- 2006
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 92(1): 270-278 (Journal)
- Registered Authors
- Incardona, John P., Linbo, Tiffany L., Scholz, Nat, Stehr, Carla
- Keywords
- zebrafish, fipronil, neurotoxicity, pesticide, GABA, glycine
- MeSH Terms
-
- Animals
- Body Size
- Immunohistochemistry
- In Situ Hybridization
- Insecticides/toxicity*
- Larva/drug effects*
- Locomotion/drug effects*
- Muscle Contraction/drug effects
- Nervous System/drug effects*
- Notochord/drug effects*
- Pyrazoles/toxicity*
- Zebrafish/embryology*
- PubMed
- 16611622 Full text @ Toxicol. Sci.
- CTD
- 16611622
Citation
Stehr, C.M., Linbo, T.L., Incardona, J.P., and Scholz, N.L. (2006) The Developmental Neurotoxicity of Fipronil: Notochord Degeneration and Locomotor Defects in Zebrafish Embryos and Larvae. Toxicological sciences : an official journal of the Society of Toxicology. 92(1):270-278.
Abstract
Fipronil is a phenylpyrazole insecticide designed to selectively inhibit insect gamma-aminobutyric acid (GABA) receptors. Although fipronil is often used in or near aquatic environments, few studies have assessed the effects of this neurotoxicant on aquatic vertebrates at sensitive life stages. We explored the toxicological effects of fipronil on embryos and larvae using the zebrafish (Danio rerio) experimental model system. Embryos exposed to fipronil at nominal concentrations at or above 0.7 microM (333 microg/L) displayed notochord degeneration, shortening along the rostral-caudal body axis, and ineffective tail flips and uncoordinated muscle contractions along the body axis in response to touch. This phenotype closely resembles zebrafish locomotor mutants of the accordion class and is consistent with loss of a reciprocal inhibitory neurotransmission by glycinergic commissural interneurons in the spinal cord. Consistent with the hypothesis that notochord degeneration may be due to abnormal mechanical stress from muscle tetany, the expression patterns of gene and protein markers specific to notochord development were unaffected by fipronil. Moreover, the degenerative effects of fipronil (1.1 microM) were reversed by co-exposure to the sodium channel blocker MS-222 (0.6 mM). The notochord effects of fipronil were phenocopied by exposure to 70 mM strychnine, a glycinergic receptor antagonist. In contrast, exposure to gabazine, a potent vertebrate GABAA antagonist, resulted in a hyperactive touch response but did not cause notochord degeneration. Although specifically developed to target insect GABA receptors with low vertebrate toxicity, our results suggest that fipronil impairs the development of spinal locomotor pathways in fish by inhibiting a structurally related glycine receptor subtype. This represents an unanticipated and potentially novel mechanism for fipronil toxicity in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping