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

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.