PUBLICATION
Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease
- Authors
- Bretaud, S., Lee, S., and Guo, S.
- ID
- ZDB-PUB-041004-18
- Date
- 2004
- Source
- Neurotoxicology and teratology 26(6): 857-864 (Journal)
- Registered Authors
- Guo, Su
- Keywords
- MPTP; Pesticides; Behavior; Dopaminergic neurons; Zebrafish; Parkinsons disease
- MeSH Terms
-
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects
- 1-Methyl-4-phenylpyridinium/toxicity
- Animals
- Behavior, Animal/drug effects
- Behavior, Animal/physiology
- Cardiovascular Abnormalities/chemically induced
- Catecholamines/metabolism
- Central Nervous System/drug effects*
- Central Nervous System/metabolism
- Central Nervous System/physiopathology
- Dose-Response Relationship, Drug
- Drug Synergism
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/physiopathology
- Larva/drug effects
- Larva/growth & development
- Motor Activity/drug effects*
- Motor Activity/genetics
- Neurons/drug effects
- Neurons/metabolism
- Neurons/pathology
- Neurotoxins/toxicity*
- Paraquat/toxicity
- Parkinson Disease, Secondary*/chemically induced
- Pigmentation/drug effects
- Pigmentation/genetics
- Rotenone/toxicity
- Zebrafish*
- PubMed
- 15451049 Full text @ Neurotoxicol. Teratol.
- CTD
- 15451049
Citation
Bretaud, S., Lee, S., and Guo, S. (2004) Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease. Neurotoxicology and teratology. 26(6):857-864.
Abstract
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra and movement defects, including bradykinesia, tremor, and postural imbalance. Whereas the etiology and pathogenesis of PD is still poorly understood, studies in animal models are providing important insights. One valuable type of animal model for PD is established by treating animals with PD-inducing neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat. These neurotoxins are thought to inhibit mitochondrial complex I activity leading to oxidative stress, impaired energy metabolism, proteasomal dysfunction, and, eventually, dopamine neuronal loss. However, the genes and pathways that underlie the neurotoxicity of these agents are not known. In this study, we explored the effect of MPTP, rotenone, and paraquat in both adult and larval zebrafish, which are highly amenable to genetic analysis that can lead to the identification of the underlying genes and pathways. Here, we report that adult zebrafish display behavioral alterations, including decreased locomotor activity in response to MPTP, whereas larval zebrafish exhibited developmental, behavioral, and DA sensitivity to these agents. Taken together, these findings suggest that zebrafish could be a valuable model for genetically dissecting the molecular mechanisms underlying the neurotoxicity of PD-inducing agents.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping