PUBLICATION
Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP
- Authors
- Lam, C.S., Korzh, V., and Strähle, U.
- ID
- ZDB-PUB-050427-2
- Date
- 2005
- Source
- The European journal of neuroscience 21(6): 1758-1762 (Journal)
- Registered Authors
- Korzh, Vladimir, Lam, Eric (C.S.), Strähle, Uwe
- Keywords
- deprenyl, diencephalon, dopamine transporter, monoamine oxidase
- MeSH Terms
-
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology*
- Animals
- Disease Susceptibility/chemically induced
- Dopamine/metabolism*
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- MPTP Poisoning/metabolism
- Motor Activity/drug effects*
- Motor Activity/physiology
- Zebrafish/embryology
- Zebrafish/metabolism
- PubMed
- 15845104 Full text @ Eur. J. Neurosci.
Citation
Lam, C.S., Korzh, V., and Strähle, U. (2005) Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. The European journal of neuroscience. 21(6):1758-1762.
Abstract
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces selective loss of dopaminergic neurons in the mammalian midbrain, eliciting symptoms characteristic of Parkinson's disease. By exploiting the advantages of zebrafish embryos, we report here that dopaminergic neurons in this species are specifically perturbed when exposed to MPTP. In contrast to mammals, the zebrafish does not possess a midbrain dopaminergic system. Instead, the main population of neurons expressing the dopamine transporter is located in the posterior tuberculum of the diencephalon. Exposure of embryos to MPTP led to a pronounced reduction in the number of dopaminergic cells in the diencephalon. This effect can be reversed by deprenyl, a specific inhibitor of monoamine oxidase B that catalyses the conversion of MPTP to its active metabolite, MPP+. Similarly, direct treatment of embryos with MPP+ abolished the diencephalic dopaminergic neurons. These larvae also demonstrated behavioural defects in swimming responses. Thus, dopaminergic neurons in the posterior tuberculum of the zebrafish may be homologous to the midbrain dopaminergic system of mammals. In addition, the mechanism behind the loss of dopaminergic neurons following pharmacological perturbation may be conserved among vertebrates and suggest that the zebrafish can be used as a convenient and economical system to study the pathogenesis of Parkinson's disease and for testing potential therapeutic strategies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping