TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation
TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation
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TRIF 在 TLR4 激活过程中促进颞叶癫痫的发生
DOI：
10.1016/j.bbi.2017.07.157
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Liu Shi-Yong
中科院分区：
文献类型：
--
作者：
Wang Fa-Xiang;Yang Xiao-Lin;Ma Yuan-Shi;Wei Yu-Jia;Yang Mei-Hua;Chen Xin;Chen Bing;He Qian;Yang Qing-Wu;Yang Hui;Liu Shi-Yong
越来越多的证据表明炎症过程在癫痫和癫痫疾病的病因病理学中发挥着至关重要的作用。含有 Toll/IL-1R 结构域的接头诱导性 IFN-β (TRIF) 激活了多种转录，导致中枢神经系统中促炎细胞因子的产生，这表明 TRIF 在癫痫发生中具有潜在作用。在这项研究中，我们研究了 TRIF 在人和小鼠致癫痫组织中的作用。 Western blot和免疫组化检测显示，人癫痫组织和小鼠模型的神经元和胶质细胞中TRIF的表达显着上调，且与癫痫发作频率呈正相关。 TRIF 表达与高迁移率组框 1 (HMGB1) 表达呈正相关。在 TRIF 缺陷小鼠中，脑电图显示癫痫发作频率和持续时间显着降低，而与野生型 (WT) 小鼠相比，KA 诱导癫痫发作。在慢性 KA 诱导的 TRIF 缺陷小鼠模型中，自发性癫痫发作的次数和持续时间也有所减少。在 TLR4 缺陷的海马神经元和小鼠模型中，在 HMGB1 和 KA 刺激期间，TRIF 表达低于 WT 小鼠。同时，在KA诱导的TRIF缺陷小鼠模型中，小胶质细胞的激活被显着抑制；促炎因子包括IL-1β、TNF-α、iNOS、HMGB1和IFN-β减少；与WT小鼠相比，海马神经元的存活率有所增加。我们的研究结果表明 TRIF 可能参与颞叶癫痫的发生，这将使其成为治疗癫痫的潜在治疗靶点。
Increasing evidence indicates that inflammatory processes play a crucial role in the etiopathology of epilepsy and seizure disorders. The Toll/IL-1R domain-containing adapter-inducing IFN-β (TRIF) activated several transcriptions leading to the production of pro-inflammatory cytokines in the central nervous system, which suggests a potential role for TRIF in the epileptogenesis of epilepsy. In this study, we investigated the roles of TRIF in human and mice epileptogenic tissues. Western blot and immunohistochemistry assays showed that the expression of TRIF was significantly upregulated in neurons and glial cells in both human epileptic tissues and mouse models, and positively correlated with seizure frequency. TRIF expression positively correlated with high-mobility group box 1 (HMGB1) expression. In TRIF-deficient mice, electroencephalograms displayed a significant decrease in seizure frequency and duration time, while KA induced seizures compared with wild-type (WT) mice. The number and duration time of spontaneous seizures were also decreased in the chronic KA-induced TRIF-deficient mouse models. In TLR4-deficient hippocampal neurons and mouse models, TRIF expression was lower compared with WT mice during HMGB1 and KA stimulation. Meanwhile, in KA-induced TRIF-deficient mouse models, microglia activation was significantly suppressed; pro-inflammatory factors including IL-1β, TNF-α, iNOS, HMGB1 and IFN-β were reduced; and the survival of the neurons in the hippocampus increased compared with WT mice. Our findings suggested that TRIF may be involved in the epileptogenesis of temporal lobe epilepsy, which would make it a potential therapeutic target for the treatment of epilepsy.
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影响因子：
9.3
作者：
Li XQ;Lv HW;Tan WF;Fang B;Wang H;Ma H
通讯作者：
Ma H
DOI：
10.1523/jneurosci.0203-12.2012
发表时间：
2012-05-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hosmane S;Tegenge MA;Rajbhandari L;Uapinyoying P;Ganesh Kumar N;Thakor N;Venkatesan A
通讯作者：
Venkatesan A
DOI：
10.1016/j.seizure.2013.04.023
发表时间：
2013-10
期刊：
Seizure
影响因子：
--
作者：
K. Pernhorst;S. Herms;P. Hoffmann;S. Cichon;H. Schulz;T. Sander;S. Schoch;A. Becker;A. Grote
通讯作者：
K. Pernhorst;S. Herms;P. Hoffmann;S. Cichon;H. Schulz;T. Sander;S. Schoch;A. Becker;A. Grote
病毒样炎症在成熟和未成熟大脑中的促发作性作用。
影响因子：
9.3
作者：
Dupuis N;Mazarati A;Desnous B;Chhor V;Fleiss B;Le Charpentier T;Lebon S;Csaba Z;Gressens P;Dournaud P;Auvin S
通讯作者：
Auvin S
影响因子：
16.2
作者：
Zhang, Chen;Atasoy, Deniz;Arac, Demet;Yang, Xiaofei;Fucillo, Marc V.;Robison, Alfred J.;Ko, Jaewon;Brunger, Axel T.;Sudhof, Thomas C.
通讯作者：
Sudhof, Thomas C.