Abstract

Objectives

Studies have extensively explored the role of microRNAs (miRs) in Parkinson’s disease (PD) and miR-185 is related to autophagy and apoptosis of dopaminergic neurons in PD. However, the role of miR-185 mediating insulin-like growth factor 1 (IGF1)/phosphatidylinositol-3-kinase/protein kinase B signalling pathway (PI3K/AKT) in PD still needs in-depth exploration.

Methods

Rat PD models were established by injection of 6-hydroxydopamine. PD rats were injected with miR-185 or insulin-like growth factor 1 (IGF1)-related sequences. Behaviour tests were performed, oxidative stress-related factors, tyrosine hydroxylase (TH)-, glial fibrillary acidic protein (GFAP)-, ionised calcium-binding adaptor molecule-1 (Iba-1)- and TUNEL-positive cells in the substantia nigra were determined. Levels of miR-185, IGF1 and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signalling pathway-related factors were also detected.

Results

miR-185 level was reduced in rats with PD. Restoring miR-185 promoted behaviour functions, ameliorated pathological damages and oxidative stress, increased TH-positive dopaminergic neurons, decreased GFAP- and Iba-1-positive cells and restrained neuronal apoptosis in the substantia nigra in PD rats. miR-185 targeted IGF1 to activate PI3K/AKT signalling pathway. Up-regulation of IGF1 mitigated restored miR-185-mediated effects on PD rats.

Conclusion

This study illustrates that miR-185 ameliorates dopaminergic neuron damage via targeting IGF1 and activating PI3K/AKT signalling pathway in PD, which renews the therapy for PD.

中文翻译：

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MicroRNA-185通过靶向帕金森病中的IGF1激活PI3K/AKT信号通路以减轻多巴胺能神经元损伤

摘要

目标

研究广泛探索了 microRNAs (miRs) 在帕金森病 (PD) 中的作用，miR-185 与 PD 中多巴胺能神经元的自噬和凋亡有关。然而，miR-185介导的胰岛素样生长因子1（IGF1）/磷脂酰肌醇-3-激酶/蛋白激酶B信号通路（PI3K/AKT）在PD中的作用仍需深入探索。

方法

通过注射6-羟基多巴胺建立大鼠PD模型。PD 大鼠被注射 miR-185 或胰岛素样生长因子 1 (IGF1) 相关序列。进行了行为测试，氧化应激相关因子、酪氨酸羟化酶 (TH)-、胶质纤维酸性蛋白 (GFAP)-、离子化钙结合接头分子-1 (Iba-1)-和黑质中的 TUNEL 阳性细胞被确定。还检测了 miR-185、IGF1 和磷脂酰肌醇-3-激酶/蛋白激酶 B (PI3K/AKT) 信号通路相关因子的水平。

结果

PD 大鼠的 miR-185 水平降低。恢复 miR-185 可促进 PD 大鼠行为功能、改善病理损伤和氧化应激、增加 TH 阳性多巴胺能神经元、减少 GFAP 和 Iba-1 阳性细胞并抑制 PD 大鼠黑质中的神经元凋亡。miR-185 靶向 IGF1 以激活 PI3K/AKT 信号通路。IGF1 的上调减轻了 miR-185 介导的对 PD 大鼠的影响。

结论

本研究表明 miR-185 通过靶向 IGF1 和激活 PD 中的 PI3K/AKT 信号通路改善多巴胺能神经元损伤，从而更新 PD 治疗。