|Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson′s Disease|
|Zhang, Li-Min1; Sun, Cong-Cong1,2; Mo, Ming-Shu1; Cen, Luan1; Wei, Lei1,3; Luo, Fei-Fei1,4; Li, Yi1,5; Li, Guo-Fei6; Zhang, Si-Yun1,7; Yi, Li7; Huang, Wei8; Liu, Zhuo-Lin1; Le, Wei-Dong9,10; Xu, Ping-Yi1,11|
|关键词||Dopamine Agonists Nurr1 Parkinson&Prime s Disease|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||ORPHAN NUCLEAR RECEPTOR ; TRANSCRIPTION FACTORS ; NURR1 EXPRESSION ; TYROSINE-HYDROXYLASE ; NURR1-DEFICIENT MICE ; LOCOMOTOR-ACTIVITY ; HETEROZYGOUS MICE ; SUBSTANTIA-NIGRA ; GENE-EXPRESSION ; MOUSE-BRAIN|
Background: Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain 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 Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.
Methods: The mRNA levels of Nurr1 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 Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 mu mol/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.
|项目编号||2007AA02Z460 ; 2011CB510001 ; 81271428 ; 81471292 ; 81430021 ; GZ20118014 ; WSTJJ20111213440802198107282218 ; 0015847A10828018|
|资助机构||National High Technology Research and Development Program of China ; State Key Development Program for Basic Research of China ; 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|
|作者单位||1.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou 510080, Guangdong, Peoples R China|
2.Shandong Univ, Qilu Affiliated Hosp, Dept Neurol, Jinan 250001, Shandong, Peoples R China
3.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou 510000, Guangdong, Peoples R China
4.Chongqing Med Univ, Peoples Hosp Chengdu 3, Affiliated Hosp 2, Dept Neurol, Chengdu 610031, Sichuan, Peoples R China
5.Jinan Univ, Guangzhou Red Cross Hosp, Dept Neurol, Guangzhou 510000, Guangdong, Peoples R China
6.Henan Univ, Huaihe Hosp, Dept Neurol, Kaifeng 470080, Henan, Peoples R China
7.Beijing Univ, Shenzhen Hosp, Dept Neurol, Shenzhen 518036, Guangdong, Peoples R China
8.Nanchang Univ, Affiliated Hosp 2, Dept Neurol, Nanchang 360006, Jiangxi, Peoples R China
9.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Neurol, Shanghai 200025, Peoples R China
10.Dalian Med Univ, Affiliated Hosp 1, Ctr Translat Res Neurol Dis, Dalian 116011, Liaoning, Peoples R China
11.Guangzhou Med Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou 510120, Guangdong, Peoples R China
|Zhang, Li-Min,Sun, Cong-Cong,Mo, Ming-Shu,et al. Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson′s Disease[J]. CHINESE MEDICAL JOURNAL,2015,128(13):1755-1760.|
|APA||Zhang, Li-Min.,Sun, Cong-Cong.,Mo, Ming-Shu.,Cen, Luan.,Wei, Lei.,...&Xu, Ping-Yi.(2015).Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson′s Disease.CHINESE MEDICAL JOURNAL,128(13),1755-1760.|
|MLA||Zhang, Li-Min,et al."Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson′s Disease".CHINESE MEDICAL JOURNAL 128.13(2015):1755-1760.|