Effects Of Pramipexole On The Circadian Rhythm Dyfunction In A 6-hydroxydopamine Treated Model Of Parkinson’s Disease

Objective:To investigate the effect of different doses of pramipexole(PPX)on the circadian dysfunction in Parkinson’s disease(PD)modelMaterials and methods:In vitro,dopaminergic cell line(PC 12 cell)was used in this study.6-Hydroxydopa(6-OHDA)and PPX were used as pharmacologic tool drugs.CCK-8 was used to detect cell viability,and real-time quantitative polymerase chain reaction(Q-PCR)was used to detect mRNA level of clock gene at different time points.Sprague-Dawley(SD)male rats at age of 6-8 weeks were divided randomly into 4 groups for animal experiments:1.sham group;2.6-OHDA group;3.6-OHDA+PPX(0.1 mg/kg);4.6-OHDA+PPX(1 mg/kg).The rat model was constructed by bilateral striatal with 6-OHDA lesion.6-OHDA rat model was injected with saline or PPX for 14 days.Rotarod test and footprint test were used to assess the motor function.Animal tissues like striatum,suprachiasmatic nucleus(SCN)and liver were collected at 6:00,12:00,18:00 and 24:00 for test.Q-PCR were used to detect the alterations of the clock gene mRNA level.And high performance liquid chromatography(HPLC)was used to measure the neurotransmitters content in the striatum.Analysis of variance was used for data analysis.Results:In vitro,after 6-OHDA treatment on PC 12 cells,the mRNA level of the clock gene at ZT12 was decreased,and the expression of the clock gene was restored to the level of the control group after PPX treatment.The motor deficits in PD rats was rescued by PPX treatment in Rotarod test and footprint test.Q PCR showed that PPX rescued clock gene expression abnormality caus(?)ly 6-OHDA treatment in SCN.In liver,low dose of PPX rescued clock gene expression abnormality caused by 6-OHDA treatment,but high dose of PPX exacerbated the abnormality.PPX has no effect on the clock gene expression in the striatum.Dopamine(DA)and 5-HT significantly reduced in 6-OHDA lesion group compared with the sham group.DA and 5-HT reduction recovered after PPX treatment.Conclusion:The circadian dysfunction of clock gene expression was confirmed in PD model.Treatment with low dose of PPX(0.1 mg/kg)can rescue circadian dysfunction in PD,but high dose of PPX(1 mg/kg)may aggravate circadian dysfunction.