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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

Li-Jun Cai1, Li Tu2, Tian Li3,4, Xiu-Lin Yang4, Yi-Pin Ren4, Ran Gu5, Qian Zhang4, Huan Yao4, Xiang Qu4, Qian Wang5, Jin-Yong Tian4
  • 1Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, PR. China
  • 2Department of General Medical, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, PR. China
  • 3Zunyi Medical University, Zunyi 563000, PR. China
  • 4Department of Emergency, Guizhou Provincial People’s Hospital, Guiyang 550004, PR. China
  • 5Department of Neurology, Guizhou Provincial People’s Hospital, Guiyang 550004, PR. China
Received: May 27, 2019Accepted: December 24, 2019Published: January 11, 2020
https://doi.org/10.18632/aging.102649

Copyright: © 2020 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.