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Pramipexole attenuates 6-OHDA-induced Parkinson’s disease by mediating the Nurr1/NF-κB pathway

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Abstract

Neuroinflammation is the key factor associated with the progression of Parkinson’s disease (PD). Pramipexole (PPX) has anti-inflammatory and antioxidant properties. This study explored the effects of PPX on PD and its related mechanisms. A PD rat model was established using 6-hydroxydopamine (6-OHDA). Thirty rats were divided into the following three groups: control, PD, and PD + PPX. The rats in the PD and PD + PPX groups were first administered 6-OHDA and then respectively treated with saline and PPX. Afterward, rotational behavior tests were performed to evaluate the efficiency of PPX. The level of tyrosine hydroxylase (TH) was measured using immunohistochemical staining. Subsequently, real-time quantitative PCR (RT-qPCR) and western blot were used to determine the expression of α-synuclein (α-syn), nuclear receptor subfamily 4 group A member 2 (Nurr1), and nuclear factor kappa B (NF-κB). PPX improved the motor behavior of PD rats caused by 6-OHDA. The number of TH-positive neurons in the PD group was significantly lower than that in the control group (P < 0.05), while PPX could rescue 6-OHDA-induced TH loss. RT-qPCR and western blot showed that Nurr1 expression was significantly downregulated in the PD group compared to that of the control group (P < 0.05), while after PPX treatment, its expression was significantly upregulated (P < 0.05). For α-syn and NF-κB, 6-OHDA significantly upregulated their expressions (P < 0.05), whereas PPX reversed them. PPX improved the motor behavior of PD through mediating the inflammatory response and regulating the Nurr1/NF-κB signaling pathway.

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Data availability

The data in the current study are available from the corresponding authors on reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (Grant Number U150322).

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Author notes

  1. Hua Gao and Dan Wang are co-first authors.

Authors and Affiliations

  1. Department of Neurology, Second Hospital Affiliated of Xinjiang Medical University, No. 38, South Lake Road, Ürümqi, 830063, Xinjiang, China

    Hua Gao, Dan Wang, Sen Jiang & Xin-Ling Yang

  2. Department of Neurology, Fifth Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830011, Xinjiang, China

    Hua Gao

  3. Cadre Health Center, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830054, Xinjiang, China

    Yu-Ling Wang

  4. Department of Neurology, Urumqi Friendship Hospital, Ürümqi, 830049, Xinjiang, China

    Jie-Ping Mao

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  1. Hua Gao
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Contributions

XY, HG, and DW designed the research study. HG, DW, JM, and YW conducted the experiments and acquired the data. SJ conducted the statistical analyses. HG and DW drafted the manuscript. XY obtained the funding and revised the manuscript. All authors have reviewed and approved the submitted version of the manuscript.

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Correspondence to Xin-Ling Yang.

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The animal experiments were approved by the Ethics Review Committee for Animal Studies of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China) and were implemented in accordance with the guidelines of animal welfare and animal experiments (IACUC 20160414-07).

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Gao, H., Wang, D., Wang, YL. et al. Pramipexole attenuates 6-OHDA-induced Parkinson’s disease by mediating the Nurr1/NF-κB pathway. Mol Biol Rep 48, 3079–3087 (2021). https://doi.org/10.1007/s11033-021-06343-8

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