AUTHOR=Yan Hai-Liang , Sun Xiao-Wen , Wang Zhi-Meng , Liu Pei-Pei , Mi Ting-Wei , Liu Cong , Wang Ying-Ying , He Xuan-Cheng , Du Hong-Zhen , Liu Chang-Mei , Teng Zhao-Qian TITLE=MiR-137 Deficiency Causes Anxiety-Like Behaviors in Mice JOURNAL=Frontiers in Molecular Neuroscience VOLUME=12 YEAR=2019 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2019.00260 DOI=10.3389/fnmol.2019.00260 ISSN=1662-5099 ABSTRACT=

Anxiety and depression are major public health concerns worldwide. Although genome-wide association studies have identified several genes robustly associated with susceptibility for these disorders, the molecular and cellular mechanisms associated with anxiety and depression is largely unknown. Reduction of microRNA-137 (miR-137) level has been implicated in the etiology of major depressive disorder. However, little is known about the in vivo impact of the loss of miR-137 on the biology of anxiety and depression. Here, we generated a forebrain-specific miR-137 knockout mouse line, and showed that miR-137 is critical for dendritic and synaptic growth in the forebrain. Mice with miR-137 loss-of-function exhibit anxiety-like behavior, and impaired spatial learning and memory. We then observe an elevated expression of EZH2 in the forebrain of miR-137 knockout mice, and provide direct evidence that knockdown of EZH2 can rescue anxious phenotypes associated with the loss of miR-137. Together our results suggest that loss of miR-137 contributes to the etiology of anxiety, and EZH2 might be a potential therapeutic target for anxiety and depressive phenotypes associated with the dysfunction of miR-137.