MicroRNA expression profiles in chronic epilepsy rats and neuroprotection from seizures by targeting miR-344a.
MicroRNA expression profiles in chronic epilepsy rats and neuroprotection from seizures by targeting miR-344a.
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慢性癫痫大鼠中的 MicroRNA 表达谱以及通过靶向 miR-344a 预防癫痫发作的神经保护
DOI：
10.2147/ndt.s141062
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发表时间：
2017
影响因子：
3.2
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Liu X;Liao Y;Wang X;Zou D;Luo C;Jian C;Wu Y
MicroRNA(MiRNA)被认为通过控制基因表达在癫痫的发生和治疗中发挥关键作用。然而，在慢性癫痫(CE)中，miRNA谱在多次长时间癫痫发作和脑损伤加重后如何变化仍不清楚。为了研究miRNA在癫痫中的作用，我们利用了戊四氮(PTZ)和海马区miRNA图谱的CE大鼠模型。用miRNA微阵列分析miRNA图谱，并与假手术组进行比较，假手术组大鼠接受相同剂量的0.9%生理盐水治疗。在CE大鼠中发现4个上调的miRNAs(miR-139-3p、-770-5p、-127-5p、-331-3p)和5个下调的miRNAs(miR-802-5p、-380-5p、-183-5p、-547-5p、-344a-5p)。通过实时定量聚合酶链式反应验证了其中三个异常的miRNAs，其结果与miRNA微阵列分析的初步结果一致。然后，侧脑室注射miR-344a单胺类化合物，然后用PTZ诱导CE模型，观察miR-344a在慢性新皮质癫痫发生中的作用。经miRNA-344a异构体和SURBLE处理后，大鼠惊厥行为恢复，皮层神经元损伤减轻。这些数据表明，miRNA-344a可能在癫痫诱导的大脑皮层细胞凋亡信号通路中具有微小的调制作用。
MicroRNA (miRNA) is believed to play a crucial role in the cause and treatment of epilepsy by controlling gene expression. However, it is still unclear how miRNA profiles change after multiple prolonged seizures and aggravation of brain injury in chronic epilepsy (CE). To investigate the role of miRNA in epilepsy, we utilized the CE rat models with pentylenetetrazol (PTZ) and miRNA profiles in the hippocampus. miRNA profiles were characterized using miRNA microarray analysis and were compared with the rats in the sham group, which received 0.9% physiological saline treatment at the same dose. Four up-regulated miRNAs (miR-139–3p, -770–5p, -127–5p, -331–3p) and 5 down-regulated miRNAs (miR-802–5p, -380–5p, -183–5p, -547–5p, -344a/-344a–5p) were found in the CE rats (fold change >1.5, P<0.05). Three of the dysregulated miRNAs were validated by quantitative real-time polymerase chain reaction, which revealed an outcome consistent with the initial results of the miRNA microarray analyses. Then, miR-344a agomir was intracerebroventricularly injected and followed by PTZ induction of CE models to investigate the effect of miR-344a in chronic neocortical epileptogenesis. After miRNA-344a agomir and scramble treatment, results showed a restoration of seizure behavior and a reduction in neuron damage in the cortex in miRNA-334a agomir treated rats. These data suggest that miRNA-344a might have a small modulatory effect on seizure-induced apoptosis signaling pathways in the cortex.