Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China; Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121001, China.
Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121001, China.
Biochem Biophys Res Commun. 2022 Oct 30;627:137-145. doi: 10.1016/j.bbrc.2022.05.038. Epub 2022 Jun 6.
The deregulation of Brain-Derived Neurotrophic Factor (BDNF) was reported to be responsible for the development of post-stroke depression (PSD), while the stimulation of the fastigial nucleus (FN) can be used to treat PDS by down-regulating the expression of miR-182 and miR-382. Therefore, we aim to test the hypothesis that the therapeutic effect of FN stimulation obtained in the treatment of PSD is mediated by the miR-382&miR-182/BDNF mRNA signaling pathways. Rat models of PSD were established and divided into sham, stroke, PSD and PSD + FNS groups to receive different treatments. Post-stroke depression-like behaviors were observed after the initiation of the treatments. TUNEL assay, Western Blot, IHC assay, real-time PCR, bioinformatics tools and luciferase assays were performed to examine the effect of FN stimulation on the expression of miR-182, miR-382 and BDNF mRNA/protein, as well as to further clarify the role of miR-382&miR-182/BDNF mRNA signaling pathways in FN stimulation. Post-stroke depression-like behaviors were significantly reduced in PSD rats. In contrary, the treatment by FN stimulation alleviated the symptoms of PSD and reduced the apoptosis index in the PSD group. Furthermore, in the PSD group, BDNF mRNA/protein levels were suppressed while the miR-382/miR-182 levels were both significantly up-regulated. After the treatment of FN stimulation, BDNF mRNA/protein levels were partly recovered, while miR-382/miR-182 levels was decreased. Furthermore, BDNF was identified as a virtual target of miR-382 and miR-182. In conclusion, FN stimulation increases the expression of BDNF via down-regulating the expression of miR-382/miR-182, thus exhibiting a positive effect in the management of PSD.
脑源性神经营养因子（BDNF）的失调被报道与卒中后抑郁（PSD）的发生有关，而刺激小脑顶核（FN）可通过下调 miR-182 和 miR-382 的表达来治疗 PSD。因此，我们旨在检验以下假说，即 FN 刺激治疗 PSD 的疗效是通过 miR-382&miR-182/BDNF mRNA 信号通路介导的。建立 PSD 大鼠模型并分为假手术、卒中、PSD 和 PSD+FNS 组接受不同的治疗。治疗开始后观察卒中后抑郁样行为。进行 TUNEL 检测、Western blot、免疫组化检测、实时 PCR、生物信息学工具和荧光素酶检测，以检查 FN 刺激对 miR-182、miR-382 和 BDNF mRNA/蛋白表达的影响，进一步阐明 miR-382&miR-182/BDNF mRNA 信号通路在 FN 刺激中的作用。PSD 大鼠的卒中后抑郁样行为明显减轻。相反，FN 刺激治疗缓解了 PSD 症状并降低了 PSD 组的细胞凋亡指数。此外，在 PSD 组中，BDNF mRNA/蛋白水平受到抑制，而 miR-382/miR-182 水平均显著上调。经 FN 刺激治疗后，BDNF mRNA/蛋白水平部分恢复，而 miR-382/miR-182 水平降低。此外，BDNF 被鉴定为 miR-382 和 miR-182 的虚拟靶标。综上所述，FN 刺激通过下调 miR-382/miR-182 的表达增加 BDNF 的表达，从而对 PSD 的管理产生积极影响。
