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

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

Cell Physiol Biochem. 2017 Sep 22;43(2):636-643

Authors: Sun J, Gao X, Meng D, Xu Y, Wang X, Gu X, Guo M, Shao X, Yan H, Jiang C, Zheng Y

Abstract
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.

PMID: 28942448 [PubMed - as supplied by publisher]

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