MicroRNA-124 Enhances Dopamine Receptor Expression and Neuronal Proliferation in Mouse Models of Parkinson’s Disease via the Hedgehog Signaling Pathway by Targeting EDN2

2019 ◽  
Vol 26 (4) ◽  
pp. 174-187 ◽  
Author(s):  
Jianfeng Wang ◽  
Wan Wang ◽  
Haiyan Zhai
2018 ◽  
Vol 51 (4) ◽  
pp. 1600-1615 ◽  
Author(s):  
Dong-Mei Wu ◽  
Shan Wang ◽  
Xin Wen ◽  
Xin-Rui Han ◽  
Yong-Jian Wang ◽  
...  

Background/Aims: Parkinson’s disease (PD) is a neurodegenerative movement disease with a high annual incidence. Accumulating evidence demonstrates that microRNAs play important roles in the pathogenesis of multiple neurological disorders, including PD. This study aims to investigate how microRNA-200a (miR-200a) regulates striatal dopamine receptor D2 (DRD2) to affect apoptosis of striatum in rats with PD and to explore the associated mechanism. Methods: After successfully establishing a PD model by 6-hydroxydopamine injections, PD rats were mainly treated with miR-200a mimics, inhibitors, Forskolin or a combination of miR-200a inhibitors and Forskolin. High-performance liquid chromatography-electrochemical detection (HPLC-ECD) was employed to detect the levels of dopamine, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and chemistry colorimetric methods were applied to detect the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). A TUNEL assay and immunocytochemical staining were performed to observe apoptosis and tyrosine hydroxylase (TH)-positive cells in the striatum. The expression of miR-200a, DRD2, Bad, Bax, Bcl-2, cAMP and PKA was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. Results: In the cellular experiments, after transfection with the inhibitor of miR-200a, decreased levels of Bax, GSH-Px, SOD, dopamine, DOPAC and HVA but increased levels of MDA and Bcl-2 were found along with a reduced apoptosis rate and increased TH-positive cell number. In addition, downregulating miR-200a resulted in lower expression of AKT, cAMP and PKA but higher expression of DRD2 and CREB, indicating that the downregulation of miR-200a increases DRD2 expression, which blocks the cAMP/PKA signaling pathway. Conclusion: This study provides evidence that the inhibition of miR-200a can repress apoptosis in the striatum via inhibition of the cAMP/PKA signaling pathway by upregulating DRD2 expression in PD rats.


Author(s):  
Yuan Gu ◽  
Xiaochen Liu ◽  
Lele Liao ◽  
Yongquan Gao ◽  
Yu Shi ◽  
...  

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