Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
BMC Neurosci. 2023 Jul 31;24(1):40. doi: 10.1186/s12868-023-00811-6.
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.
先前的研究表明，电刺激小脑绒球核（FNS）可显著减少脑缺血后的梗死体积并改善神经功能恢复。然而，FNS 的神经保护作用的分子机制仍不清楚。
在本研究中，我们建立了一个包括 1 小时 FNS 后再灌注 3、6、12、24 和 72 小时的大鼠缺血/再灌注模型。通过转录组测序在五个不同时间点获得脑组织中分子变化的表达谱。利用 Allen Brain Atlas、STRING 数据库和 Cytoscape 软件注释 miRNA 表达模式和核心基因的功能和途径，以探讨 FNS 介导的神经保护机制。
结果表明，FNS 与神经递质循环途径有关。FNS 可能通过靶向核心 Dlg4 基因对应的 miRNAs 调节突触小泡中单胺神经递质的释放，通过 APA 事件刺激抗凋亡作用，刺激小脑、皮层/丘脑等脑区神经元的相互激活，调节神经血管耦联，减少脑损伤。
FNS 可能通过核心 Dlg4 基因及其对应的转录因子和蛋白激酶的甲基化，调节突触小泡中神经递质的释放，激活神经元和神经血管耦联，从而诱导 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。
