title: Inhibition of miR-203 Reduces Spontaneous Recurrent Seizures in Mice.
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.
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Advanced Neural Technologies, Seoul, South Korea.
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. stemcell.snu@gmail.com.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea. stemcell.snu@gmail.com.|Department of Neurology, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul, 110-744, South Korea. stemcell.snu@gmail.com.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.
authors.forename: Jangsup
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.|Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.
authors.forename: Junsang
authors.initials: J
authors.lastname: Sunwoo
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|The Armed Forces Capital Hospital, Bundang, South Korea.
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. sangkun2923@gmail.com.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea. sangkun2923@gmail.com.|Department of Neurology, Seoul National University Hospital, 101, Daehak-ro, Jongro-gu, Seoul, 110-744, South Korea. sangkun2923@gmail.com.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004827:Epilepsy / Q000235:genetics / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D012008:Recurrence; D012640:Seizures / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C575934:MIRN203 microRNA, mouse; D035683:MicroRNAs; D021122:Protein Subunits; D018009:Receptors, Glycine
keywords: Antagomir; Epilepsy; Glycine receptor-beta; Spontaneous recurrent seizure; microRNA