Short-term Memory Defects And Emotional Changes Following Sleep Deprivation In A Rotenone Treated Zebrafish Model Of Parkinson's Disease

Study Objectives : Parkinson's disease(PD)is the second most common neurodegenerative disorder in the world.Apart from motor deficits,PD reduces the patient's quality of life through sleep disturbances,cognitive impairment and emotional disorders.However,it's unclear whether bad life habits such as stay up late exacerbate the patient's cognition and emotional disorders.Thus we investigated the long-term consequences of sleep deprivation on short-term memory and emotion using a rotenone treated zebrafish model of Parkinson's disease.Materials and methods: Wild-type male zebrafish at age of 4 month were control fish were sleep deprived for 24 h.We evaluated the influence of sleep deprivation on motor function,short-term memory and emotional changes through locomotor activity,object discrimination task and light-dark box respectively.Rotenone and sleep deprivation-induced abnormality was measured by Western Blot,HPLC and Q-PCR.Results:Behavioral assays,using locomotor activity assay,there was no obvious difference between rotenone treated and control fish in the duration of freezing and swimming activity at a slow speed.However,the rotenone treated fish showed a reduction in swimming duration and distance traveled at a fast speed compared with control fish.But sleep deprivation had no effect on locomotor activity.Meanwhile,we observed that TH expression decreased by 30% in rotenone treated fish,but no further TH changes after sleep deprivation.The object discrimination task exhibited that the short-term cognitive deficits of rotenone treated fish are more serious than the control fish after sleep deprivation.Light-dark box test showed that rotenone treated fish are more dysphoric than the control fish after sleep deprivation.Dopamine and DOPAC significantly reduced in rotenone treated fish compared with the untreated control fish.However,this DOPAC reduction recovered after sleep deprivation.The expression of drd 2a,drd 2b,drd 2c and drd 3 in rotenone treated zebrafish elevated compared with untreated control group and sleep deprivation group.However,the rotenone treated zebrafish manifested a decrease level of D2 and D3 after sleep deprivation.Drd 1a and drd 1b did not show any significantly changes among the four groups.Conclusion:Our findings suggest that zebrafish treated with rotenone may have a more severe damage of memory and emotional function after sleep deprivation,which may be related to the changes in the DA systems.