背景:卒中后抑郁(PSD)是卒中后常见的精神症状。莫罗尼赛德,一种在山茱萸中发现的环烯醚萜苷,因其缓解抑郁症相关症状的潜力而引起了极大的关注。
目的:本研究旨在强调莫诺苷在治疗PSD中的潜在用途,并阐明其潜在的分子机制。
方法:为了建立可靠的PSD模型,将雄性C57BL/6小鼠与CUMS联合进行短暂的MCAO。莫罗尼塞德管理后,神经元活力,通过Nissl染色和TUNEL检测评估海马细胞凋亡,分别。使用SPT评估抑郁样行为,TST,和FST。使用Longa评分和圆柱体测试来评估莫诺苷对运动功能的影响。此外,为了研究潜在的分子机制,进行生物信息学分析和双荧光素酶测定以研究MiR-409-3p-BDNF的相互作用。此外,在通过AAV病毒过表达MiR-409-3p之后,我们使用RT-qPCR评估了BDNF/TrkB信号通路中关键成分的mRNA表达和蛋白质水平,免疫组织化学,和蛋白质印迹分析。
结果:观察到的凋亡减少和抑郁样行为的改善强烈表明莫诺苷作为PSD治疗剂的潜力。此外,皮质中BDNF/TrkB信号通路内关键蛋白的上调表明莫罗尼苷激活了该通路.通过生物信息学分析,MiR-409-3p被鉴定并发现与BDNF基因结合,导致BDNF表达的抑制。重要的是,我们证明莫诺苷减轻了MiR-409-3p对BDNF的抑制作用,从而促进BDNF/TrkB信号通路的激活。
结论:研究结果表明,莫罗尼苷能通过MiR-409-3p介导的BDNF/TrkB信号通路改善PSD症状。这些结果强调了BDNF信号通路在改善PSD症状中的重要性,并为莫诺苷治疗PSD提供了可能的机制。
BACKGROUND: Post-stroke depression (PSD) is a common psychiatric symptom after a stroke. Morroniside, an iridoid glycoside found in Cornus officinalis, has garnered significant attention for its potential to alleviate symptoms associated with depression.
OBJECTIVE: This study aims to highlight the potential use of morroniside in the treatment of PSD and elucidate the underlying molecular mechanisms.
METHODS: To establish a reliable PSD model, male C57BL/6 mice were subjected to brief MCAO in conjunction with CUMS. Post-morroniside administration, neuronal viability, and hippocampal cell apoptosis were evaluated by Nissl staining and TUNEL detection, respectively. Depression-like behaviors were evaluated using SPT, TST, and FST. The Longa score and cylinder test were used to evaluate the effect of morroniside on motor function. Furthermore, to investigate the underlying molecular mechanisms, bioinformatic analysis and the dual luciferase assay were performed to investigate the MiR-409-3p-BDNF interaction. In addition, subsequent to MiR-409-3p overexpression via AAV virus, we assessed mRNA expression and protein levels of key components within the BDNF/TrkB signaling pathway using RT-qPCR, immunohistochemistry, and western blot analysis.
RESULTS: The observed decrease in apoptosis and amelioration of depression-like behaviors strongly indicate the potential of morroniside as a therapeutic agent for PSD. Furthermore, the upregulation of key proteins within the BDNF/TrkB signaling pathway in the cortex suggests that morroniside activates this pathway. Through bioinformatics analysis, MiR-409-3p was identified and found to bind to the BDNF gene, resulting in the inhibition of BDNF expression. Importantly, we demonstrate that morroniside mitigates this inhibitory effect of MiR-409-3p on BDNF, thereby facilitating the activation of the BDNF/TrkB signaling pathway.
CONCLUSIONS: The findings suggest that morroniside demonstrates the ability to improve PSD symptoms through the BDNF/TrkB signaling pathway mediated by MiR-409-3p. These results emphasize the importance of the BDNF signaling pathway in improving PSD symptoms and provide a possible mechanism for morroniside to treat PSD.