Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP

Autor: Chen Sok Lam, Vladimir Korzh, Uwe Strähle
Přispěvatelé: Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Embryo
Nonmammalian
animal structures
Dopamine
Population
MESH: Disease Susceptibility
MESH: Dopamine
Motor Activity
MESH: MPTP Poisoning
Midbrain
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Dopaminergic Cell
Animals
Neurotoxin
MESH: Animals
education
MESH: Zebrafish
Zebrafish
030304 developmental biology
Dopamine transporter
0303 health sciences
education.field_of_study
biology
General Neuroscience
MPTP
Dopaminergic
fungi
MPTP Poisoning
MESH: Embryo
Nonmammalian
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
biology.organism_classification
MESH: Motor Activity
chemistry
nervous system
1-Methyl-4-phenyl-1
2
3
6-tetrahydropyridine
embryonic structures
MESH: 1-Methyl-4-phenyl-1
2
3
6-tetrahydropyridine
biology.protein
Disease Susceptibility
Neuroscience
030217 neurology & neurosurgery
Zdroj: European Journal of Neuroscience
European Journal of Neuroscience, Wiley, 2005, 21 (6), pp.1758-62. ⟨10.1111/j.1460-9568.2005.03988.x⟩
ISSN: 0953-816X
1460-9568
DOI: 10.1111/j.1460-9568.2005.03988.x⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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