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: Soon-Tae Lee, Daejong Jeon, Kon Chu, Keun-Hwa Jung, Jangsup Moon, Junsang Sunwoo, Dong-Kyu Park, Hyunwoo Yang, Ji-Hyun Park, Manho Kim, Jae-Kyu Roh, Sang Kun Lee
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 54 Issue 5 Pg. 3300-3308 (07 2017) ISSN: 1559-1182 [Electronic] United States
• PMID: 27165289 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN203 microRNA, mouse
• MicroRNAs
• Protein Subunits
• Receptors, Glycine

Topics

• Animals
• Chronic Disease
• Epilepsy (genetics, pathology)
• Male
• Mice, Inbred C57BL
• MicroRNAs (genetics, metabolism)
• Protein Subunits (metabolism)
• Receptors, Glycine (metabolism)
• Recurrence
• Seizures (genetics)
• Up-Regulation (genetics)