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.
Highlights
Parkinson’s disease is a neurodegenerative disorder mainly affecting the elderly
Significant progress has been made in parkinsonian neurodegeneration, which is primarily due to an in-depth understanding of the mechanisms of action of toxins, such as 6-hydroxydopamine (6-OHDA), rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, or others [4]. 6-OHDA is a neurotoxin that causes dopamine neuronal death and is commonly used to establish experimental models of Parkinson’s disease in rodents [5]
The Parkinson’s disease rat models were established by injection of 6-OHDA in two points of the right medial forebrain bundle to explore the role of miR-375 and specificity protein 1 (SP1) in pathological behaviors of 6-OHDA-induced Parkinson’s disease rats
Summary
Parkinson’s disease is a neurodegenerative disorder mainly affecting the elderly. It is characterized by progressive damage to automatic behavior resulting in hypokinesia, sensory neglect and rigidity [1]. 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. 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 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
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