Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease by inhibiting SP1.

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.

• Authors: Li-Jun Cai, Li Tu, Tian Li, Xiu-Lin Yang, Yi-Pin Ren, Ran Gu, Qian Zhang, Huan Yao, Xiang Qu, Qian Wang, Jin-Yong Tian
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 1 Pg. 672-689 (01 11 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 31927536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autophagy-Related Proteins
• Sp1 Transcription Factor

Topics

• Animals
• Autophagy-Related Proteins (genetics, metabolism)
• Disease Models, Animal
• Dopaminergic Neurons (metabolism)
• Gene Expression Regulation
• Inflammation (genetics, metabolism, pathology)
• Oxidative Stress (genetics)
• Parkinson Disease (genetics, metabolism)
• Rats
• Sp1 Transcription Factor (metabolism)
• Substantia Nigra (metabolism)