Studies on sensitivity of zebrafish as a model organism for Parkinson's disease: Comparison with rat model

Abstract

Objective: To determine the utility of zebra fish as an animal model for Parkinson's disease (PD) in comparison with rat model.

Materials and methods: MTT assay was performed on rat and zebrafish brain synaptosomal fractions using rotenone as a neurotoxic agent. Quercetin and resveratrol were used as standards to compare anti-apoptotic activity in both organisms. Catalepsy was induced in zebrafish by exposing them to haloperidol (9 μM) solution. Drug-treated groups were exposed to bromocriptine and pramipexole, 30 min prior to haloperidol exposure at the dose of 2, 5, and 10 μg/mL. Swimming speed, time spent in the bottom of the tank, and complete cataleptic time were evaluated to assess behavioral changes. In rats, catalepsy was induced using haloperidol (1.25 mg/kg i.p.). Drug-treated groups received bromocriptine (2.5 mg/kg.) and pramipexole (1 mg/kg) orally. Bar test, block test, and locomotor activity were carried out to assess behavioral changes.

Results: Resveratrol and quercetin showed comparable inhibition of apoptosis in rats and zebrafish. In anti-cataleptic study, bromocriptine and pramipexole-treated groups showed significant difference (P < 0.05) in behavioral parameters as compared to haloperidol control group in both the experimental organisms. Results obtained from fish model were in correlation with rat model.

Conclusion: Findings of the present study revealed that zebrafish model is highly sensitive and can be used for basic screening of drugs against PD.

Keywords: 3-[4,5-dimethylthia zol-2-yl]-2; 5-diphenyltetrazolium bromide; Catalepsy; zebrafish.

Figure 1

Examination tank used for behavioral evaluations

Figure 2

Estimate of percentage viability in MTT assay using quercetin and resverotrol where, PC=Rotenone Control, NC=Vehicle control, Q5=Quercetin 5 μg/mL, Q10=Quercetin 10 μg/mL, R5=Resverotrol 5 μg/ mL, R10=Resverotrol 10 μg/mL. All values are expressed in % viability of control n=3 for rats, n=50 for zebrafish. *Rotenone control group was found to be significantly (P<0.05) different from vehicle control group. **Treatment groups were found to be significantly (P < 0.05) different as compared to rotenone control group

Figure 3

Induction of Catalepsy in zebrafish in haloperidol solution: (a) Fish just introduced in haloperidol solution (b) Aberrant swimming patterns shown by fish after some time (c) State of complete catalepsy