The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice
- 102 Downloads
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.
KeywordsAnxiety-like behavior miR-150 Hippocampus Stress Synaptic plasticity
We wish to thank Xin-Fu Zhou from the University of South Australia for his critical reading of the manuscript.
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.
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).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
Consent for Publication
Ethics Approval and Consent to Participate
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.
- Alsharafi WA, Xiao B, Li J (2016) MicroRNA-139-5p negatively regulates GluN2A-containingNMDA receptor in the ratpilocarpine model andpatientswith temporal lobeepilepsy. Full-Length Orig Res 57:1931–1940Google Scholar
- Barber BA, Kohl KL, Nancy KA, Jeffrey I. Gold (2014) Acute stress, depression, and anxiety symptoms among English and Spanish speaking children with recent trauma exposure. HHS Public Access, 21:66–71Google Scholar
- Choi GH, Ko KH, Kim JO, Kim JW, Oh SH, Han IB, Cho KG, Kim OJ, Bae J, KimNK (2016) Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke. Int J Mol Med, 1:345–356Google Scholar
- Fan JM, Ding L, Dm X, Dy C, Jiang P, Ge W, Zhao R, Guo J, Xf F, Xue F, Wang Y, Mao S, Hu L, Gong Y (2017) Amelioration of apelin-13 in chronic normobaric hypoxia-inducedanxiety-likebehavior is associated with an inhibition of NF-κB in thehippocampus. Brain Res Bull 130:67–74PubMedCrossRefGoogle Scholar
- Li BJ, Liu P, Chu Z, Shang Y, Huan MX, Dang YH, Gao CG (2017) Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1,and dopamine receptor 2. Neuropharmacology 8:1–7Google Scholar
- Lima-ojeda JM, Voqt MA, Pfeiffer N, Dormann C, Köhr G, Sprengel R, Gass P, Inta D (2013) Pharmacological blockade of GluN2B-containing NMDA receptors induces antidepressant-like effects lacking psychotomimetic action and neurotoxicity in the perinatal and adult rodent brain. Prog Neuro-Psychopharmacol Biol Psychiatry 45:28–33CrossRefGoogle Scholar
- Shepard R, Coutellier L (2017) Changes in the prefrontal glutamatergic and parvalbumin systems of mice exposed to unpredictable chronic stress. Mol NeurobiolGoogle Scholar
- Siegel (2012) Pharmacology biochemistry and behavior, vol 100, pp 653–655Google Scholar
- Wang HT, Huang FL, Hu ZL, Zhang WJ, Qiao XQ, Huang YQ, Dai RP, Li F, Li CQ (2017) Early-life social isolation-induced depressive-like behavior in rats results in microglial activation and neuronal histone methylation that are mitigated by minocycline. Neurotox Res 31(4):505–520PubMedCrossRefGoogle Scholar
- Wittmann A, Schlagenhauf F, John T, Guhn A, Rehbein H, Siegmund A, Stoy M, Held D, Schulz I, Fehm L et al (2001) A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. Eur Arch Psychiatry Clin Neurosci 3:185–194Google Scholar
- Wohleb ES, McKim DB, Shea DT, Powell ND, Tarr AJ, Sheridan JF, Godbout JP (2014) Re-establishment of anxiety in stress-sensitized mice is caused by monocyte trafficking from the spleen to the brain. A RCHIVAL R EPORT 75:970–981Google Scholar
- Zhao HB, Jiang YM, Li XJ, Liu YY, Bai XH, Li N, Chen JX, Liu Q, Yan ZY, Zhao FZ (2017) Xiao Yao San improves the anxiety-like behaviors of rats induced by chronic immobilization stress: the involvement of the JNK signaling pathway in the hippocampus. Biol Pharm Bull 40:187–194PubMedCrossRefGoogle Scholar