Antagomirs Targeting MicroRNA-134 Increase Limk1 Levels After Experimental Seizures in Vitro and in Vivo

Background: MiR-134 is enriched in dendrites of hippocampal neurons and plays crucial roles in the progress of epilepsy. The present study aims to investigate the effects of antagomirs targeting miroRNA-134 (Ant-134) on limk1 expression and the binding of miR-134 and limk1 in experimental seizure. M...

Full description

Bibliographic Details
Main Authors: Jiahang Sun, Xiaoying Gao, Dawei Meng, Yang Xu, Xichun Wang, Xin Gu, Mian Guo, Xiaodong Shao, Hongwen Yan, Chuanlu Jiang, Yongri Zheng
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2017-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/480647
Description
Summary:Background: MiR-134 is enriched in dendrites of hippocampal neurons and plays crucial roles in the progress of epilepsy. The present study aims to investigate the effects of antagomirs targeting miroRNA-134 (Ant-134) on limk1 expression and the binding of miR-134 and limk1 in experimental seizure. Methods: Status epilepticus (SE) rat model was established by lithium chloride-pilocarpine injection and was treated with Ant-134 by intracerebroventricular injection. Low Mg2+-exposed primary neurons were used as an in vitro model of SE. The expression of miR-134 was determined using real-time PCR. Protein expressions of limk1 and cofilin were determined by Western blotting. Luciferase reporter assay was used to examine the binding between miR-134 and limk1 3’-untranslated region. Results: The expression of miR-134 was markedly enhanced in hippocampus of the SE rats and low Mg2+-exposed neurons. Ant-134 increased the expression of limk1 and reduced the expression of cofilin in the SE hippocampus and Low Mg2+-exposed neurons. In addition, luciferase reporter assay confirmed that miR-134 bound limk1 3’-UTR. MiR-134 overexpression inhibited limk1 mRNA and protein expressions in neurons. Conclusion: Blockage of miR-134 upregulates limk1 expression and downregulated cofilin expression in hippocampus of the SE rats. This mechanism may contribute to the neuroprotective effects of Ant-134.
ISSN:1015-8987
1421-9778