Department of Neurology, PLA 960 Hospital, Zibo, Shandong, 255300, China.
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450014, China.
Brain Res Bull. 2021 Jan;166:92-101. doi: 10.1016/j.brainresbull.2020.10.019. Epub 2020 Nov 1.
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).
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.
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.
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.
帕金森病（PD）是一种神经系统的常见退行性疾病，其发病机制尚未明确。本研究通过调节 LIM 和 SH3 结构域蛋白 1（LASP1），探讨微小 RNA（miR）-218-5p 对 PD 大鼠黑质（SN）中多巴胺能神经元损伤的保护作用。
采用 6-羟多巴胺定点注射建立 PD 大鼠模型。采用 miR-218-5p 过表达重组腺相关病毒（rAAV）或 LASP1 沉默 rAAV 对 PD 大鼠 SN 中的多巴胺能神经元进行干预，探讨其作用。观察 SN 病理结构的变化，检测 SN 中酪氨酸羟化酶（TH）和脱乙酰基 vindoline 乙酰转移酶（DAT）的表达、SN 中多巴胺能神经元凋亡和氧化应激因子的变化。检测 SN 中 miR-218-5p、LASP1、Bcl-2 和 Bax 的表达。验证 miR-218-5p 与 LASP1 的靶向关系。
PD 大鼠脑 SN 中存在 miR-218-5p 下调和 LASP1 过表达。上调 miR-218-5p 或抑制 LASP1 可改善 PD 大鼠脑 SN 中多巴胺能神经元的病理损伤，增加脑 SN 中 TH 和 DAT 阳性细胞数。此外，上调 miR-218-5p 或抑制 LASP1 可抑制 PD 大鼠脑 SN 中多巴胺能神经元的凋亡和氧化应激。另外，上调 miR-218-5p 可抑制 PD 大鼠脑 SN 中 LASP1 的表达。LASP1 是 miR-218-5p 的直接靶标。
本研究表明，上调 miR-218-5p 可改善 PD 大鼠多巴胺能神经元损伤，与抑制 LASP1 有关。
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