Exp Neurobiol.  2020 Apr;29(2):138-149. 10.5607/en19072.

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

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


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.


MIR137; KCC2; Anxiety; Potassium
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