Objective

Parkinson’s disease (PD) is a frequent degenerative disease of the nervous system with undefined pathogenesis. This study explored the protective effect of microRNA (miR)-218−5p on dopaminergic neuron injury in substantia nigra (SN) of rats with PD through the regulation of LIM and SH3 domain protein 1 (LASP1).

Methods

The PD rat model was established by fixed point injection of 6-hydroxydopamine into the rats. The PD rats were injected with miR-218−5p overexpressed recombinant adeno-associated virus (rAAV) or LASP1 silenced rAAV to explore their roles in dopaminergic neurons in SN of rats with PD. The changes in pathological structure of SN were observed and the expression of tyrosine hydroxylase (TH) and deacetylvindoline acetyltransferase (DAT), the dopaminergic neuron apoptosis and oxidative stress factor in the SN were detected. The expression of miR-218−5p, LASP1, Bcl-2 and Bax in SN was detected. The targeting relationship between miR-218−5p and LASP1 was confirmed.

Results

Declined miR-218−5p and overexpressed LASP1 existed in the brain SN of PD rats. Up-regulated miR-218−5p or inhibited LASP1 improved the pathological damage of dopaminergic neurons and increased the number of TH and DAT positive cells in brain SN of PD rats. Furthermore, elevated miR-218−5p or depressed LASP1 inhibited the apoptosis, and oxidative stress of dopaminergic neurons in brain SN of PD rats. In addition, increased miR-218−5p repressed the expression of LASP1 in the brain SN of PD rats. LASP1 was proven to be a direct target of miR-218−5p.

Conclusion

The study highlights that up-regulated miR-218−5p could improve the damage of dopaminergic neurons in PD rats, which was related to the inhibition of LASP1.

中文翻译：

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上调 microRNA-218-5p 通过抑制 LASP1 改善帕金森病大鼠多巴胺能神经元的损伤

客观的

帕金森病 (PD) 是一种常见的神经系统退行性疾病，发病机制不明。本研究通过调控 LIM 和 SH3 结构域蛋白 1 (LASP1) 探讨 microRNA (miR)-218-5p 对 PD 大鼠黑质 (SN) 多巴胺能神经元损伤的保护作用。

方法

大鼠定点注射6-羟基多巴胺建立PD大鼠模型。给 PD 大鼠注射 miR-218-5p 过表达的重组腺相关病毒 (rAAV) 或 LASP1 沉默的 rAAV，以探索它们在 PD 大鼠 SN 中多巴胺能神经元中的作用。观察SN的病理结构变化，检测SN中酪氨酸羟化酶(TH)和去乙酰文多林乙酰转移酶(DAT)的表达、多巴胺能神经元凋亡和氧化应激因子的表达。检测 SN 中 miR-218-5p、LASP1、Bcl-2 和 Bax 的表达。证实了 miR-218-5p 和 LASP1 之间的靶向关系。

结果

PD 大鼠脑 SN 中存在 miR-218-5p 下降和 LASP1 过表达。上调 miR-218-5p 或抑制 LASP1 可改善多巴胺能神经元的病理损伤，增加 PD 大鼠脑 SN 中 TH 和 DAT 阳性细胞的数量。此外，升高的 miR-218-5p 或抑制 LASP1 抑制了 PD 大鼠脑 SN 中多巴胺能神经元的细胞凋亡和氧化应激。此外，增加的 miR-218-5p 抑制了 PD 大鼠脑 SN 中 LASP1 的表达。LASP1 被证明是 miR-218-5p 的直接靶标。

结论

该研究强调，上调miR-218-5p可以改善PD大鼠多巴胺能神经元的损伤，这与抑制LASP1有关。