Antagomirs Targeting MiroRNA-134 Attenuates Epilepsy in Rats through Regulation of Oxidative Stress, Mitochondrial Functions and Autophagy.
Antagomirs Targeting MiroRNA-134 Attenuates Epilepsy in Rats through Regulation of Oxidative Stress, Mitochondrial Functions and Autophagy.
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靶向 MiroRNA-134 的 Antagomirs 通过调节氧化应激、线粒体功能和自噬减轻大鼠癫痫
DOI：
10.3389/fphar.2017.00524
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发表时间：
2017
影响因子：
5.6
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Sun J;Gao X;Meng D;Xu Y;Wang X;Gu X;Guo M;Shao X;Yan H;Jiang C;Zheng Y
现有的抗癫痫药物对近三分之一的癫痫患者效果不佳。MiR-134咪达唑仑预防匹鲁卡品诱导的癫痫持续状态。在这项研究中，建立了氯化锂-匹罗卡品诱导的癫痫持续状态模型，并通过侧脑室注射靶向miR-134的阿托莫西米（Ant-134）进行治疗。Ant-134处理显著改善大鼠在Morris水迷宫测试中的表现，抑制齿状回中的苔藓纤维发芽，并增加海马CA 1区的存活神经元。miR-134的沉默显著降低了海马中的丙二醛和4-羟基壬烯醛水平，并增加了超氧化物歧化酶活性。与癫痫持续状态大鼠相比，Ant-134治疗还显著增加了海马中ATP的产生和线粒体呼吸酶复合物的活性，并显著降低了活性氧的产生。最后，Ant-134处理显著下调海马自噬相关蛋白Atg 5、beclin-1和轻链3B的表达。总之，Ant-134通过抑制氧化应激、改善线粒体功能和调节海马中的自噬来减轻癫痫。
The effects of the existing anti-epileptic drugs are unsatisfactory to almost one third of epileptic patients. MiR-134 antagomirs prevent pilocarpine-induced status epilepticus. In this study, a lithium chloride-pilocarpine-induced status epilepticus model was established and treated with intracerebroventricular injection of antagomirs targeting miR-134 (Ant-134). The Ant-134 treatment significantly improved the performance of rats in Morris water maze tests, inhibited mossy fiber sprouting in the dentate gyrus, and increased the survival neurons in the hippocampal CA1 region. Silencing of miR-134 remarkably decreased malonaldehyde and 4-hydroxynonenal levels and increased superoxide dismutase activity in the hippocampus. The Ant-134 treatment also significantly increased the production of ATP and the activities of mitochondrial respiratory enzyme complexes and significantly decreased the reactive oxygen species generation in the hippocampus compared with the status epilepticus rats. Finally, the Ant-134 treatment remarkably downregulated the hippocampal expressions of autophagy-associated proteins Atg5, beclin-1 and light chain 3B. In conclusion, Ant-134 attenuates epilepsy via inhibiting oxidative stress, improving mitochondrial functions and regulating autophagy in the hippocampus.
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影响因子：
6
作者：
Gallagher LE;Williamson LE;Chan EY
通讯作者：
Chan EY
影响因子：
3.1
作者：
Jimenez-Mateos, Eva M.;Engel, Tobias;Henshall, David C.
通讯作者：
Henshall, David C.
影响因子：
4.7
作者：
Jacobson, J;Duchen, MR;Heales, SJR
通讯作者：
Heales, SJR
microRNA、自噬和癫痫之间联系的评估
影响因子：
4.1
作者：
Gan, Jing;Qu, Yi;Mu, Dezhi
通讯作者：
Mu, Dezhi
影响因子：
14.5
作者：
Kann, O;Kovács, R;Heinemann, U
通讯作者：
Heinemann, U