Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2
| Autor: | Xuan-Cheng He, Shuang-Feng Zhang, Cong Liu, Ting-Wei Mi, Hong-Zhen Du, Zhao-Qian Teng, Zhi-Meng Wang, Xiao-Wen Sun, Chang-Mei Liu, Ying-Ying Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene knockdown business.industry KCC2 Antagonist Anxiety medicine.disease MIR137 03 medical and health sciences Cellular and Molecular Neuroscience 030104 developmental biology 0302 clinical medicine Autism spectrum disorder Schizophrenia Knockout mouse microRNA Potassium Medicine Original Article Neurology (clinical) Bipolar disorder business Neuroscience 030217 neurology & neurosurgery Homeostasis |
| Zdroj: | Experimental Neurobiology |
| ISSN: | 2093-8144 1226-2560 |
| DOI: | 10.5607/en19072 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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