| Literature DB >> 27165289 |
Soon-Tae Lee1,2, Daejong Jeon1,3, Kon Chu4,5,6, Keun-Hwa Jung1,2, Jangsup Moon1,2, Junsang Sunwoo1,2,7, Dong-Kyu Park1, Hyunwoo Yang8, Ji-Hyun Park1, Manho Kim1,2, Jae-Kyu Roh1,9, Sang Kun Lee10,11,12.
Abstract
Inhibitory synaptic receptors are dysfunctional in epileptic brains, and agents that selectively target these receptors may be effective for the treatment of epilepsy. MicroRNAs interfere with the translation of target genes, including various synaptic proteins. Here, we show that miR-203 regulates glycine receptor-β (Glrb) in epilepsy models. miR-203 is upregulated in the hippocampus of epileptic mice and human epileptic brains and is predicted to target inhibitory synaptic receptors, including Glrb. In vitro transfection, target gene luciferase assays, and analysis of human samples confirmed the direct inhibition of GLRB by miR-203, and AM203, an antagomir targeting miR-203, reversed the effect of miR-203. When intranasal AM203 was administered, AM203 reached the brain and restored hippocampal GLRB levels in epileptic mice. Finally, intranasal AM203 reduced the epileptic seizure frequency of mice. Overall, this study suggests that GLRB expression in the epileptic brain is controlled by miR-203, and intranasal delivery of AM203 showed therapeutic effects in chronic epilepsy mice.Entities:
Keywords: Antagomir; Epilepsy; Glycine receptor-beta; Spontaneous recurrent seizure; microRNA
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Year: 2016 PMID： 27165289 DOI： 10.1007/s12035-016-9901-7
Source DB: PubMed Journal: Mol Neurobiol ISSN： 0893-7648 Impact factor: 5.590