Silencing MicroRNA-155 Attenuates Kainic Acid-Induced Seizure by Inhibiting Microglia Activation
Silencing MicroRNA-155 Attenuates Kainic Acid-Induced Seizure by Inhibiting Microglia Activation
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沉默 MicroRNA-155 通过抑制小胶质细胞激活来减轻红藻氨酸诱导的癫痫发作
DOI：
10.1159/000496344
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Zheng, Honghua
中科院分区：
文献类型：
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作者：
Fu, Huajun;Cheng, Yiyun;Zheng, Honghua
目的：神经炎症是癫痫发作和癫痫发展的重要因素。micro-RNA-155（miR-155）在免疫和炎症中起着关键作用。本研究旨在探讨miR-155及其介导的炎症在癫痫中的作用。方法：将约8周龄的雄性C57 BL/6小鼠腹腔注射（i. p.）红藻氨酸（KA）（15 mg/kg）或盐水。KA组小鼠发生急性癫痫发作后，进一步进行侧脑室注射（i. c. v.）或miR-155 miR-155 miR-155 miR-155。根据Racine's量表观察动物行为，并记录脑电图。培养原代小神经胶质细胞，并用Escheromir NC或Escheromir处理。采用全细胞电生理技术检测不同条件培养液处理后神经元的自发性EPSC和IPSC。通过qRT-PCR在这些模型中以及癫痫患者和健康对照的脑或血液中检测到miR-155。结果如下：与神经元相比，miR-155在胶质细胞中大量表达，并且其在癫痫患者和KA诱导的癫痫发作小鼠的脑中的表达显著升高。沉默miR-155减弱KA诱导的癫痫发作、异常脑电图、促炎细胞因子表达和小胶质细胞形态学改变。此外，来自KA处理的小胶质细胞的条件培养基损害神经元兴奋性，而来自KA和miR-155 Atomir共处理的小胶质细胞的条件培养基没有这种作用。最后，癫痫患者血液中的miR-155水平显著高于健康对照组。结论（s）：这些发现表明miR-155的异常上调通过诱导小胶质细胞神经炎症而促成癫痫发生。
Objective(s): Neuroinflammation is an important contributor to the development of seizures and epilepsy. Micro-RNA-155 (miR-155) plays a critical role in immunity and inflammation. This study aims to explore the function of miR-155 and miR-155-mediated inflammation in epilepsy. Methods: About 8-week-old male C57BL/6 mice were administered an intraperitoneal injection (i.p.) of kainic acid (KA) (15 mg/kg) or saline. The mice in the KA group developing acute seizure were further subjected to intracerebroventricular injection (i.c.v.) of antagomir negative control (NC) or miR-155 antagomir. Animal behavior was observed according to Racine’s scale, and electroencephalographs were recorded. Primary microglia were cultured and treated with antagomir NC or antagomir. Whole-cell electrophysiological recording was conducted to detect the spontaneous EPSCs and IPSCs in the neurons treated with different conditioned medium from those microglia. miR-155 were detected by qRT-PCR in those models, as well as in the brain or blood from epileptic patients and healthy controls. Results: miR-155 was abundantly expressed in glial cells compared with neurons, and its expression was markedly elevated in the brain of epilepsy patients and KA-induced seizure mice. Silencing miR-155 attenuated KA-induced seizure, abnormal electroencephalography, proinflammatory cytokine expression, and microglia morphology change. Moreover, conditioned media from KA-treated microglia impaired neuron excitability, whereas conditioned media from KA and miR-155 antagomir co-treated microglia had no such effects. Finally, miR-155 levels were significantly higher in the blood of epilepsy patients than those of healthy controls. Conclusion(s): These findings demonstrate that aberrant upregulation of miR-155 contributes to epileptogenesis through inducing microglia neuroinflammation.