The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China.
Wannan Medical College, Wuhu, 241002, Anhui, China.
Mol Neurobiol. 2024 Dec;61(12):10339-10354. doi: 10.1007/s12035-024-04192-7. Epub 2024 May 9.
Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.
Helicid (HEL) 已被发现具有抗抑郁的药理学活性。本文旨在证明 HEL 通过调节 lncRNA-NONRATT030918.2 来发挥抗抑郁作用的确切分子机制，从而在抑郁模型中发挥抗抑郁作用。通过慢性不可预测轻度应激 (CUMS) 刺激建立大鼠抑郁模型，并通过行为实验评估大鼠的抑郁状态。此外，建立了皮质酮 (CORT) 诱导的 PC12 细胞体外模型，并通过 CCK8 测试细胞活性。通过荧光原位杂交实验证实 NONRATT030918.2 分子的亚细胞定位。通过双荧光素酶报告基因检测、RNA 结合蛋白免疫沉淀检测和 RNA 下拉检测分析 NONRATT030918.2 与 miRNA-128-3p 和 Prim1 之间的关系。使用 Q-PCR 检测 NONRATT030918.2、miRNA-128-3p 和 Prim1 的水平。此外，通过 Western blot 检测 Prim1、Bax、Bcl-2 和 caspase3 的水平。HEL 可以减轻 CUMS 大鼠的抑郁样行为（P<0.05），并通过下调 NONRATT030918.2 的水平来降低海马体的死亡率（P<0.05）。在 CORT 诱导的 PC12 细胞中，HEL 的干预导致 NONRATT030918.2 和 Prim1 的表达降低（P<0.05），而 miRNA-128-3p 的表达增加（P<0.05）。这表明 HEL 通过调节 NONRATT030918.2 的表达来上调 miRNA-128-3p（P<0.05），从而通过靶向 Prim1 抑制 CORT 诱导的 PC12 细胞凋亡（P<0.05）。NONRATT030918.2/miRNA-128-3p/Prim1 轴可能是 HEL 发挥神经保护作用的关键调节网络。
