当前位置: X-MOL 学术Neurochem. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The Mechanism of SNHG8/Microrna-421-3p/Sorting Nexin 8 Axis on Dopaminergic Neurons in Substantia Nigra in a Mouse Model of Parkinson's Disease
Neurochemical Research ( IF 4.4 ) Pub Date : 2022-11-18 , DOI: 10.1007/s11064-022-03795-7
Siwei Zhou 1 , Xiaofang Zhou 1 , Zewen Jiang 2 , Jinrong Ma 1 , Yuanmei Li 1 , Zhiyong Qian 1 , Hua Li 1
Affiliation  

Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting the aging population. Particularly, long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in PD, while the role of lncRNA SNHG8 in PD remains to be further explored. C57BL/6 mice were induced by rotenone to establish a PD model in vivo, and then the dopaminergic (DA) neuronal damage and locomotor dysfunction in rotenone-treated mice were evaluated. Murine DA cell line MN9D was treated with rotenone to establish a cellular PD model in vitro. Then, the viability, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells were assessed. Expression levels of SNHG8, microRNA-421-3p (miR-421-3p), and sorting nexin 8 (SNX8) in the substantia nigra (SN) of PD mice and rotenone-treated MN9D cells were detected. The interaction between SNHG8 and miR-421-3p, and the targeting relationship between SNX8 and miR-421-3p were confirmed. SNHG8 and SNX8 expression levels were decreased while miR-421-3p expression level was increased in the SN of PD mice and rotenone-treated MN9D cells. Upregulated SNHG8 ameliorated dopaminergic neuron damage and locomotor dysfunction in PD mice. Meanwhile, upregulated SNHG8 enhanced viability, diminished apoptosis, and alleviated mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells. Mechanistically, SNHG8 bound to miR-421-3p, and miR-421-3p targeted SNX8. Overexpressed SNHG8 downregulates miR-421-3p to alleviate rotenone-induced dopaminergic neuron injury in PD via upregulating SNX8.



中文翻译:

SNHG8/Microrna-421-3p/Sorting Nexin 8 轴对帕金森病小鼠黑质多巴胺能神经元的作用机制

帕金森病 (PD) 是一种影响人口老龄化的进行性神经退行性疾病。特别是,长链非编码 RNA (lncRNA) 已被证明在 PD 中发挥重要作用,而 lncRNA SNHG8 在 PD 中的作用仍有待进一步探索。鱼藤酮诱导C57BL/6小鼠在体内建立PD模型,然后评估鱼藤酮处理小鼠的多巴胺能(DA)神经元损伤和运动功能障碍。用鱼藤酮处理小鼠 DA 细胞系 MN9D 以建立体外细胞 PD 模型。然后,评估鱼藤酮处理的 MN9D 细胞的活力、细胞凋亡、线粒体功能障碍、内质网应激和自噬。SNHG8、microRNA-421-3p (miR-421-3p)、并检测了 PD 小鼠黑质 (SN) 中的连接蛋白 8 (SNX8) 和鱼藤酮处理的 MN9D 细胞。确认了 SNHG8 与 miR-421-3p 之间的相互作用,以及 SNX8 与 miR-421-3p 之间的靶向关系。在 PD 小鼠和鱼藤酮处理的 MN9D 细胞的 SN 中,SNHG8 和 SNX8 表达水平降低,而 miR-421-3p 表达水平增加。上调 SNHG8 可改善 PD 小鼠的多巴胺能神经元损伤和运动功能障碍。同时,上调 SNHG8 可增强经鱼藤酮处理的 MN9D 细胞的活力,减少细胞凋亡,并减轻线粒体功能障碍、内质网应激和自噬。从机制上讲,SNHG8 与 miR-421-3p 结合,而 miR-421-3p 靶向 SNX8。

更新日期:2022-11-20
down
wechat
bug