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Original Article

Exp Neurobiol 2020; 29(2): 138-149

Published online April 30, 2020

© The Korean Society for Brain and Neural Sciences

Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2

Ting-Wei Mi1,2†, Xiao-Wen Sun1,3†, Zhi-Meng Wang1,3†, Ying-Ying Wang1,3†, Xuan-Cheng He1,2†, Cong Liu1,3, Shuang-Feng Zhang1,4, Hong-Zhen Du1,2, Chang-Mei Liu1,2,3* and Zhao-Qian Teng1,2,3*

1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, 2Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, 3Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, 4School of Life Sciences, University of Science and Technology of China, Hefei 230026, China

Correspondence to: *To whom correspondence should be addressed.
Zhao-Qian Teng, TEL: 86-10-82619699, FAX: 86-10-64807099
Chang-Mei Liu, TEL: 86-10-82619690, FAX: 86-10-64807316
These authors equally contributed to this work.

Received: November 3, 2019; Revised: April 29, 2020; Accepted: May 1, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
( which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

Graphical Abstract

Keywords: MIR137, KCC2, Anxiety, Potassium