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The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice

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Abstract

Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.

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Acknowledgments

We wish to thank Xin-Fu Zhou from the University of South Australia for his critical reading of the manuscript.

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81471372 to Fang Li, Grant No. 31371212 to Chang-Qi Li), the Natural Science Foundation of Hunan Province, China (Grant No. 2018JJ3635 to Fang Li), and the Science and Technology Projects of Hunan Province (Grant No. 2014wk 3025 to Rong Hu).

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WZ performed behavioral testing and Western blot RT-PCR experiments and wrote the manuscript. WC was involved in data collection and data analysis. YH, YC, BT, LW, GZ, YL, and ZH participated in data collection and data analysis. RH and CL provided experimental suggestions and assisted in writing the manuscript. The corresponding authors XX and FL supervised, designed the project, interpreted the work, revised the manuscript, and provided funds. All authors contributed to the study and have approved the final manuscript.

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Correspondence to Xiao-Wei Xing or Fang Li.

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All animal procedures performed in this study were reviewed and approved by the Animal Care and Use Committee of Central South University and were conducted in accordance with the guidelines of the International Association for the Study of Depression.

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Zhang, WJ., Cao, WY., Huang, YQ. et al. The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice. Neurotox Res 35, 160–172 (2019). https://doi.org/10.1007/s12640-018-9943-x

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