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Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

摘要Background:Nurr1 plays an essential role in the development,survival,and function maintenance ofmidbrain dopaminergic (DA) neurons,and it is a potential target for Parkinson's disease (PD).Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs),but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive.This study aimed to measure the Nurrl mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.Methods:The mRNA levels of Nurrl in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured.The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC,as well as the subgroups of PD.Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale,age,and drug treatments.Besides,the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.Results:The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010),respectively.Furthermore,the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group.Multivariate linear regression showed DA agonists,L-dopa,and DA agonists were independent predictors correlated with Nurrl mRNA expression level in PBMC.In vitro,in the cultured PBMC treated with 10 μmol/L pramipexole,the Nurr1 mRNA levels were significantly increased by 99.61%,71.75%,73.16% in 2,4,and 8 h,respectively (P < 0.001).Conclusions:DA agonists can induce Nurr1 expression in PBMC,and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

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作者单位 Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China [1] Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China ;Department of Neurology, Qilu Affiliated Hospital of Shandong University, Jinan, Shandong 250001, China [2] Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China ;Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510000, China [3] Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China ;Department of Neurology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong 510000, China [4]
栏目名称 Original Articles
DOI 10.4103/0366-6999.159349
发布时间 2015-08-05
基金项目
grants from the National High Technology Research and Development Program of China the State Key Development Program for Basic Research of China the National Natural Science Foundation of China key project from Guangzhou Science and Technology Department Medical Scientific Research Foundation of Guangdong Province,China Medicine and Health Care Technology Projects Foundation of Guangzhou City,China
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中华医学杂志(英文版)

中华医学杂志(英文版)

2015年128卷13期

1755-1760页

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