先前的研究表明,电刺激小脑顶核(FNS)可以显着减少脑缺血后的梗死体积并改善神经功能恢复。然而,FNS神经保护作用的分子机制尚不明确。
在这项研究中,我们建立了大鼠缺血/再灌注模型,包括1hFNS,然后再灌注3、6、12、24和72h。通过在五个不同时间点的转录组测序获得脑组织中分子改变的表达谱。AllenBrainAtlas对miRNA表达模式和核心基因的功能和通路进行了注释,STRING数据库和Cytoscape软件,从而探讨FNS介导的神经保护作用机制。
结果表明FNS与神经递质周期通路相关。FNS可能通过核心Dlg4基因靶向相应的miRNAs来调节突触小泡中单胺神经递质的释放,刺激选择性多腺苷酸化(APA)事件对大脑的抗凋亡作用,并刺激小脑中神经元的相互作用激活,皮质/丘脑和其他大脑区域,调节神经血管耦合,减少脑损伤。
FNS可能通过调节核心Dlg4基因和相应的转录因子和蛋白激酶的甲基化来调节突触小泡中神经递质的释放,从而激活神经元和神经血管的偶联,诱导APA事件的抗凋亡机制。我们的研究结果为脑组织对FNS驱动的神经保护的反应方式提供了新的视角。
Previous studies have demonstrated that electrical stimulation of the cerebellar fastigial nucleus (FNS) can considerably decrease infarction volume and improve neurofunction restoration following cerebral ischemia. Nevertheless, the molecular mechanism of the neuroprotective effect of FNS is still vague.
In this study, we developed a rat model of ischemia/reperfusion that included 1 h FNS followed by reperfusion for 3, 6, 12, 24, and 72 h. The expression profile of molecular alterations in brain tissues was obtained by transcriptome sequencing at five different time points. The function and pathway of miRNA expression pattern and core genes were annotated by Allen Brain Atlas, STRING database and Cytoscape software, so as to explore the mechanism of FNS-mediated neuroprotection.
The results indicated that FNS is associated with the neurotransmitter cycle pathway. FNS may regulate the release of monoamine neurotransmitters in synaptic vesicles by targeting the corresponding miRNAs through core
Dlg4 gene, stimulate the Alternative polyadenylation (APA) incident\'s anti -apoptosis effect on the brain, and stimulate the interaction activation of neurons in cerebellum, cortex/thalamus and other brain regions, regulate neurovascular coupling, and reduce cerebral damage.
FNS may activate neuronal and neurovascular coupling by regulating the release of neurotransmitters in synaptic vesicles through the methylation of core
Dlg4 gene and the corresponding transcription factors and protein kinases, inducing the anti-apoptotic mechanism of APA events. The findings from our investigation offer a new perspective on the way brain tissue responds to FNS-driven neuroprotection.