PUBLICATION

Neurochemical and behavioural changes in zebrafish Danio rerio after systemic administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Authors
Anichtchik, O.V., Kaslin, J., Peitsaro, N., Scheinin, M., and Panula, P.
ID
ZDB-PUB-040109-31
Date
2004
Source
Journal of neurochemistry   88(2): 443-453 (Journal)
Registered Authors
Anichtchik, Oleg, Kaslin, Jan, Panula, Pertti, Peitsaro, Nina
Keywords
behavior, dopamine, histamine, noradrenaline
MeSH Terms
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology*
  • Animals
  • Brain/drug effects*
  • Brain/metabolism
  • Dopamine/metabolism
  • Female
  • Injections, Intramuscular
  • Male
  • Motor Activity/drug effects*
  • Motor Activity/physiology
  • Norepinephrine/metabolism
  • Oxidopamine/pharmacology*
  • Pilot Projects
  • Zebrafish/metabolism*
PubMed
14690532 Full text @ J. Neurochem.
Abstract
Dopaminergic deficiency in the brain of zebrafish was produced by systemic administration of two catecholaminergic neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the neurochemical and behavioural changes were characterized. The levels of dopamine and noradrenaline decreased significantly after the injection of MPTP and 6-OHDA. Corresponding to these changes, fish exhibited characteristic changes in locomotor behaviour, i.e. the total distance moved and velocity decreased after both neurotoxins. Tyrosine hydroxylase and caspase 3 protein levels were not altered after MPTP or 6-OHDA injections, as studied by immunohistochemistry and western blotting. The catecholaminergic cell clusters suggested to correspond to the mammalian nigrostriatal cell group displayed normal tyrosine hydroxylase immunoreactivity after the toxin treatment and did not show signs of DNA fragmentation that would indicate activation of cascades that lead to cell death. The results show that single systemic injections of MPTP and 6-OHDA induce both biochemical and behavioural changes in zebrafish, albeit failing to produce any significant morphological alteration in catecholaminergic cell clusters at the tested doses. This approach may be used for the screening of chemicals affecting the dopaminergic system. The model may be especially useful for evaluation of the role of novel genes in neurotoxicity, as a large number of zebrafish mutants are becoming available.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping