Image_1_MiR-137 Deficiency Causes Anxiety-Like Behaviors in Mice.pdf (83.5 kB)
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Image_1_MiR-137 Deficiency Causes Anxiety-Like Behaviors in Mice.pdf

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posted on 30.10.2019, 08:29 by Hai-Liang Yan, Xiao-Wen Sun, Zhi-Meng Wang, Pei-Pei Liu, Ting-Wei Mi, Cong Liu, Ying-Ying Wang, Xuan-Cheng He, Hong-Zhen Du, Chang-Mei Liu, Zhao-Qian Teng

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.