Abstract:  Objective    To investigate the impacts of okadaic acid (OA) on the neurological function and behavior of zebrafish larvae, and explore the possible application of zebrafish as an animal model in the study of neurodegenerative diseases. Methods    Zebrafish larvae at 3 days post fertilization (3 dpf) stage was treated with 0.05 µmol/L, 0.10 µmol/L, and 0.20 µmol/L OA respectively for 7 days. The survival rate of zebrafish larvae was calculated, the swimming track within 30 min was acquired by behaviroral analysis system, and the swimming trajectory, swimming distance and inactive time were recorded. The expression levels of protein phosphatase 2A (PP2A) and nicotinic acetylcholine receptor alpha 7 (α7-nAChR) genes were tested by real-time fluorescent quantitative PCR.  Results    After 7 days of treatment, the survival rate and swimming trajectory of the zebrafish larvae in 0.05 µmol/L and 0.10 µmol/L OA treatment groups were not significantly different from those in the control group (P>0.05). Zebrafish larvae treated with 0.20 µmol/L OA for 7 days showed inactive swimming, reduced swimming distance and prolonged sluggish time with significant difference as compared with the control group (P<0.05). The expression level of PP2A gene was down-regulated significantly in 0.20 µmol/L OA treatment group (P<0.05), however the expression level of α7-nAChR was not affected (P>0.05).  Conclusion   The treatment with 0.20 µmol/L OA for 7 days can cause the abnormal neurological function and behavior of zebrafish larvae. 

Key words: Zebrafish, Okadaic acid, Neurodegenerative disease, Protein phosphatase 2A; Nicotinic acetylcholine receptor alpha 7