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.

Dopamine D2Receptor Activity Modulates Akt Signaling and Alters GABAergic Neuron Development and Motor Behavior in Zebrafish Larvae

“…We next asked whether reducing the levels of endogenous DA would result in an increase or decrease in movement episodes. To address this question we used the DA neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which can either cause a defect in DA function by decreasing overall levels of tyrosine hydroxylase (TH) expression (Anichtchik et al, 2004) or by killing DA neurons (Lam et al, 2005;McKinley et al, 2005;Panula et al, 2010). Using our experimental parameters, we treated 3 dpf zebrafish with MPTP for 2 d (replenished once per day).…”

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

“…Most neurotoxins, such as MPTP, 6-hydroxydopamine (OHDA) and rotenone, are known to induce DA neuron loss in animal models. Zebrafish PD models have been well validated and zebrafish develop relevant PD pathological conditions in response to these toxins (24)(25)(26). Moreover, exposure of zebrafish to neurotoxins induces relevant clinical behavioural features of PD reflected by reduced swimming velocity and total distance moved.…”

Zebrafish and motor control over the last decade

“…Dopamine, serotonergic, noradrenergic and histamatergic systems in larvae and/or adults have been described morphologically and some receptors and trasnporters have been cloned (Boehmler et al, 2004;Kaslin and Panula, 2001;Ma, 2003;McLean and Fetcho, 2004a;McLean and Fetcho, 2004b;Wang et al, 2006)}. Pharmacological studies, mutants, and chemical ablations indicate important roles for neuromodulatory systems, but mechanistic studies to reveal the activity patterns of neurodmodulatory neurons and their affects on motor circuits are needed (Anichtchik et al, 2004;Brustein et al, 2003a;Rink and Guo, 2004).…”