Research Paper Volume 12, Issue 1 pp 672—689
Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson’s disease by inhibiting SP1
- 1 Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, PR. China
- 2 Department of General Medical, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, PR. China
- 3 Zunyi Medical University, Zunyi 563000, PR. China
- 4 Department of Emergency, Guizhou Provincial People’s Hospital, Guiyang 550004, PR. China
- 5 Department of Neurology, Guizhou Provincial People’s Hospital, Guiyang 550004, PR. China
Received: May 27, 2019 Accepted: December 24, 2019 Published: January 11, 2020
https://doi.org/10.18632/aging.102649How to Cite
Abstract
Background: This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson’s disease through down-regulating transcription factor specificity protein 1 (SP1).
Results: The successfully modeled rats with Parkinson’s disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson’s disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson’s disease.
Conclusion: Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson’s disease by inhibiting SP1.
Methods: Parkinson’s disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson’s disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson’s disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.