Parkinson's disease (PD) is a complex neurodegenerative disease in which the understanding of the underlying molecular mechanisms can be constructive in the diagnosis and treatment. Matrix metalloproteinase (MMPs) elevation and damage to the blood–brain barrier (BBB) are critical mechanisms involved in the PD separation. Studies have revealed that changes in miR-149-5p and CoQ10 are associated with BBB damage, and CoQ10 can affect the levels of some miRs. Hence, in the present study, we aimed to evaluate CoQ10 and miR-149-5p mimic on miR-149-5p, MMPs and TH expression, and behavioral functions of the PD models. PD was induced by injection of 6-OHDA into the rats' Medial Forbrain Bundle (MFB). The behavioral tests, including the Rotation test, Rotarod test, and Open field test, have been directed two weeks after PD induction. Next, the MiR-149-5p mimic (miR-mimic) and CoQ10 have been administered to rats. The same behavioral tests have been evaluated two weeks after administration to investigate the effect of miR-149-5p mimic and CoQ10. The rats were followed extra four weeks, and the behavioral tests have performed again. Finally, the expression of MMPs and miR-149-5p genes was measured using RT-qPCR, and tyrosine hydroxylase (TH) was assessed through immunohistochemistry analysis. According to the obtained results, the level of miR-149-5p has decreased, followed by PD induction in rats. RT-qPCR analysis has represented upregulation and downregulation of miR-149-5p and MMP-2,9, respectively, after miR-mimic and CoQ10 treatment. The treated rats have also represented improved motor function and increased TH + cells in the striatum according to the behavioral tests and immunohistochemistry assay. Taking together miR-149 and CoQ10 has shown to have an impressive potential to prevent damage to dopaminergic neurons caused by 6-OHDA injection through reducing MMP-2,9, increased TH expression, and improved motor function.

帕金森病 (PD) 是一种复杂的神经退行性疾病，对潜在分子机制的理解对诊断和治疗具有建设性意义。基质金属蛋白酶 (MMP) 升高和血脑屏障 (BBB) 损伤是 PD 分离的关键机制。研究表明，miR-149-5p 和 CoQ10 的变化与 BBB 损伤有关，CoQ10 可以影响一些 miRs 的水平。因此，在本研究中，我们旨在评估 CoQ10 和 miR-149-5p 模拟物对 miR-149-5p、MMP 和 TH 表达以及 PD 模型的行为功能的影响。通过将 6-OHDA 注射到大鼠的内侧前脑束 (MFB) 中诱导 PD。行为测试，包括旋转测试、Rotarod 测试和旷场测试，已在 PD 诱导两周后进行。下一个，已将 MiR-149-5p 模拟物 (miR-mimic) 和 CoQ10 施用于大鼠。在给药两周后评估了相同的行为测试，以研究 miR-149-5p 模拟物和 CoQ10 的效果。对大鼠进行了额外的四个星期的跟踪，并且再次进行了行为测试。最后，使用 RT-qPCR 测量 MMP 和 miR-149-5p 基因的表达，并通过免疫组织化学分析评估酪氨酸羟化酶 (TH)。根据获得的结果，miR-149-5p的水平已经降低，随后是大鼠的PD诱导。RT-qPCR 分析分别代表了 miR-mimic 和 CoQ10 处理后 miR-149-5p 和 MMP-2,9 的上调和下调。根据行为测试和免疫组织化学测定，经处理的大鼠还表现出改善的运动功能和纹状体中的 TH + 细胞增加。将 miR-149 和 CoQ10 结合使用已显示出通过减少 MMP-2,9、增加 TH 表达和改善运动功能来预防由 6-OHDA 注射引起的多巴胺能神经元损伤的巨大潜力。