期刊
NEUROBIOLOGY OF STRESS
卷 14, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ynstr.2021.100311
关键词
Post-traumatic stress disorder; miR-132; MeCP2; BDNF; Anxiety-like behavior
资金
- National Natural Science Foundation of China [31900850]
- Educational Commission of Liaoning Province, China [QN2019024]
- National Undergraduate Innovation and Entrepreneurship Training Program [202010159029]
In this study, miR-132 was found to be involved in the formation of anxiety-like symptoms in adult rat PTSD models by targeting MeCP2, with its effects related to the BDNF/TrkB and its downstream ERK and Akt signaling pathways. These findings suggest that targeting miR-132 may provide a potential therapeutic strategy for PTSD.
Post-traumatic stress disorder (PTSD) is usually accompanied by anxiety symptoms and decreased expression of brain-derived neurotrophic factor (BDNF), which played an important role in promoting neuronal proliferation and survival. Methyl CpG-binding protein 2 (MeCP2) is a positive mediator of BDNF and is regulated by miR-1323p. In the present study, we explored the possible molecular mechanism of miR-132, focusing on the involvement of MeCP2 and BDNF in the formation of anxiety-like symptoms of PTSD. Single prolonged stress (SPS) was used to establish a model of PTSD in adult rats and the anxiety-like behavior was tested by the elevated plus-maze (EPM). The level of miR-132 in the prefrontal cortex (PFC) was increased and intraventricular injection of anti-miR-132 could significantly improve the anxiety-like behavior of rats exposed to SPS through MeCP2 and the subsequent upregulation of BDNF levels. Then tropomyosin-related kinase B (TrkB) and downstream signals, including MAP kinase ERK1/2 and phosphoinositol 3-kinase (PI3K)/Akt pathways, were activated by BDNF upregulation, and might participate in regulating dendritic complexity and the expression of postsynaptic density-95 (PSD95) and synapsin I in the PFC of SPS rats. Furthermore, we found that the apoptosis of cells in PFC induced by SPS procedure could be alleviated by miR-132 inhibition. Our results suggest that miR-132 might be involved in the formation of anxiety-like symptoms of adult rat PTSD models by targeting MeCP2, and this effect is related to BDNF/TrkB and its downstream ERK and Akt signaling pathways.
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