title: Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease.
abstract: 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 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.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhang
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: Sun
authors.forename: Ming-Shu
authors.initials: MS
authors.lastname: Mo
authors.forename: Luan
authors.initials: L
authors.lastname: Cen
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Guo-Fei
authors.initials: GF
authors.lastname: Li
authors.forename: Si-Yun
authors.initials: SY
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Yi
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Zhuo-Lin
authors.initials: ZL
authors.lastname: Liu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Le
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080; Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong 510120, China.
authors.forename: Ping-Yi
authors.initials: PY
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018491:Dopamine Agonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger