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Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease
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 a...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733729/ https://www.ncbi.nlm.nih.gov/pubmed/26112716 http://dx.doi.org/10.4103/0366-6999.159349 |
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author | Zhang, Li-Min Sun, Cong-Cong Mo, Ming-Shu Cen, Luan Wei, Lei Luo, Fei-Fei Li, Yi Li, Guo-Fei Zhang, Si-Yun Yi, Li Huang, Wei Liu, Zhuo-Lin Le, Wei-Dong Xu, Ping-Yi |
author_facet | Zhang, Li-Min Sun, Cong-Cong Mo, Ming-Shu Cen, Luan Wei, Lei Luo, Fei-Fei Li, Yi Li, Guo-Fei Zhang, Si-Yun Yi, Li Huang, Wei Liu, Zhuo-Lin Le, Wei-Dong Xu, Ping-Yi |
author_sort | Zhang, Li-Min |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4733729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47337292016-04-04 Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease Zhang, Li-Min Sun, Cong-Cong Mo, Ming-Shu Cen, Luan Wei, Lei Luo, Fei-Fei Li, Yi Li, Guo-Fei Zhang, Si-Yun Yi, Li Huang, Wei Liu, Zhuo-Lin Le, Wei-Dong Xu, Ping-Yi Chin Med J (Engl) Original Article 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. Medknow Publications & Media Pvt Ltd 2015-07-05 /pmc/articles/PMC4733729/ /pubmed/26112716 http://dx.doi.org/10.4103/0366-6999.159349 Text en Copyright: © 2015 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Zhang, Li-Min Sun, Cong-Cong Mo, Ming-Shu Cen, Luan Wei, Lei Luo, Fei-Fei Li, Yi Li, Guo-Fei Zhang, Si-Yun Yi, Li Huang, Wei Liu, Zhuo-Lin Le, Wei-Dong Xu, Ping-Yi Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease |
title | Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease |
title_full | Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease |
title_fullStr | Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease |
title_full_unstemmed | Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease |
title_short | Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease |
title_sort | dopamine agonists exert nurr1-inducing effect in peripheral blood mononuclear cells of patients with parkinson's disease |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733729/ https://www.ncbi.nlm.nih.gov/pubmed/26112716 http://dx.doi.org/10.4103/0366-6999.159349 |
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