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Silencing MicroRNA-155 Attenuates Kainic Acid-Induced Seizure by Inhibiting Microglia Activation.
Neuroimmunomodulation ( IF 2.2 ) Pub Date : 2019-03-29 , DOI: 10.1159/000496344
Huajun Fu 1, 2, 3 , Yiyun Cheng 1, 2, 4 , Haijuan Luo 1, 2 , Zhouyi Rong 2 , Yanfang Li 2 , Ping Lu 2, 5 , Xiaowen Ye 1, 2 , Weiyan Huang 2, 6 , Ziguo Qi 2, 6 , Xiuying Li 2, 6 , Baoying Cheng 2 , Xintian Wang 1, 2, 4 , Yi Yao 7 , Yun-Wu Zhang 2 , Weihong Zheng 1, 4 , Honghua Zheng 8, 9
Affiliation  

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.

中文翻译:

沉默MicroRNA-155通过抑制小胶质细胞活化来减轻海因酸诱导的癫痫发作。

目的神经炎症是癫痫发作和癫痫发展的重要因素。微小RNA-155(miR-155)在免疫和炎症中起关键作用。这项研究旨在探讨miR-155和miR-155介导的炎症在癫痫中的功能。方法大约8周大的雄性C57BL / 6小鼠腹膜内注射(ip)海藻酸(KA)(15 mg / kg)或生理盐水。KA组发生急性癫痫发作的小鼠进一步接受脑室内注射antagomir阴性对照(NC)或miR-155 antagomir。根据拉辛氏量表观察动物行为,并记录脑电图仪。培养原代小胶质细胞并用antagomir NC或antagomir处理。进行全细胞电生理记录以检测用来自那些小胶质细胞的不同条件培养基处理的神经元中的自发EPSC和IPSC。通过qRT-PCR在这些模型以及癫痫患者和健康对照组的大脑或血液中检测到miR-155。结果与神经元相比,miR-155在神经胶质细胞中大量表达,在癫痫患者和KA诱发的癫痫小鼠的大脑中其表达明显升高。沉默miR-155可减轻KA诱发的癫痫发作,脑电图异常,促炎细胞因子表达和小胶质细胞形态变化。此外,来自KA处理的小胶质细胞的条件培养基会损害神经元兴奋性,而来自KA和miR-155 antagomir共处理的小胶质细胞的条件培养基则没有这种作用。最后,癫痫患者血液中的miR-155水平显着高于健康对照者。结论这些发现表明,miR-155的异常上调通过诱导小胶质细胞神经炎症而促进癫痫发生。
更新日期:2019-11-01
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