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

• Published in: Cellular physiology and biochemistry Vol. 43; no. 2; pp. 636 - 643
• Main Authors: Sun, Jiahang, Gao, Xiaoying, Meng, Dawei, Xu, Yang, Wang, Xichun, Gu, Xin, Guo, Mian, Shao, Xiaodong, Yan, Hongwen, Jiang, Chuanlu, Zheng, Yongri
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Animals; Antagomirs - therapeutic use; Cells, Cultured; Cofilin; Convulsions & seizures; Epilepsy; Genetic Therapy; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Kinases; Lim Kinases - genetics; Limk1; Male; Memory; MicroRNAs; MicroRNAs - genetics; MiR-134; Morphology; Neurons; Neurons - metabolism; Neurons - pathology; Neurosciences; Original Paper; Physiology; Protein expression; Proteins; Rats, Sprague-Dawley; Rodents; Seizures - genetics; Seizures - pathology; Seizures - therapy; Status Epilepticus - genetics; Status Epilepticus - pathology; Status Epilepticus - therapy; Up-Regulation; United States > US; China; Cofilin; Epilepsy; Limk1; MiR-134; Hippocampus
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000480647

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 Mg 2+ -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 Mg 2+ -exposed neurons. Ant-134 increased the expression of limk1 and reduced the expression of cofilin in the SE hippocampus and Low Mg 2+ -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.