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心理应激诱导前额叶皮质中精神药理学 mRNA 和 microRNA 谱的改变与应激易感性和应激弹性有关。

Revision to psychopharmacology mRNA and microRNA profiles are associated with stress susceptibility and resilience induced by psychological stress in the prefrontal cortex.

机构信息

School of Pharmacy, Qingdao University, 38 Dengzhou, Qingdao, 266021, Shandong, China.

University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Psychopharmacology (Berl). 2020 Oct;237(10):3067-3093. doi: 10.1007/s00213-020-05593-x. Epub 2020 Jun 26.

Abstract

OBJECTIVES

The prefrontal cortex is associated with many mental neurological diseases. The mRNA and microRNA profiles of stress susceptibility and resilience induced by psychological stress in the prefrontal cortex remain to be elucidated.

METHODS

The C57 observer was placed in the cage next to the CD1 mouse and suffered psychological stress by watching the CD1 attacking another C57 mouse. After 5 days of psychological stress, the degree of fear memory and anxiety of mice were measured by social interaction test and elevated plus maze (EPM). The prefrontal cortex was extracted and mRNA and microRNA profiles were analyzed by high-throughput sequencing.

RESULTS

In susceptible mice versus resilient mice, the downregulation of genes involved in serotonergic synapse may be related to the susceptibility to psychological stress. The imbalanced regulation of genes involved in VEGF, p53, chemokine, Ras, sphingolipid, GnRH, MAPK, and NOD-like receptor signaling pathways may be related to the susceptibility to psychological stress. Compared with control mice, susceptible mice and resilient mice have changed genes involved in serotonergic synapse, neuroactive ligand-receptor interaction, axon guidance, calcium, cAMP, GnRH, estrogen, PI3K-Akt, MAPK, Rap1, and Ras signaling pathways, these changes may be related to psychological stress processing. The sequencing results of mRNAs and microRNAs were verified by qRT-PCR and dual-luciferase reporter assay.

CONCLUSIONS

The downregulation of genes involved in serotonergic synapse and imbalance of signaling pathways in the prefrontal cortex may be related to susceptibility to psychological stress.

摘要

目的

前额叶皮层与许多精神神经系统疾病有关。心理应激引起的前额叶皮层应激易感性和弹性的 mRNA 和 microRNA 谱仍有待阐明。

方法

将 C57 观察者置于 CD1 小鼠旁边的笼子中,通过观看 CD1 攻击另一只 C57 小鼠而遭受心理压力。经过 5 天的心理压力后,通过社交互动测试和高架十字迷宫(EPM)测量小鼠的恐惧记忆和焦虑程度。提取前额叶皮层,通过高通量测序分析 mRNA 和 microRNA 谱。

结果

与弹性小鼠相比,易感小鼠中涉及 5-羟色胺能突触的基因下调可能与对心理应激的易感性有关。涉及 VEGF、p53、趋化因子、Ras、鞘脂、GnRH、MAPK 和 NOD 样受体信号通路的基因的不平衡调节可能与对心理应激的易感性有关。与对照小鼠相比,易感小鼠和弹性小鼠改变了涉及 5-羟色胺能突触、神经活性配体-受体相互作用、轴突导向、钙、cAMP、GnRH、雌激素、PI3K-Akt、MAPK、Rap1 和 Ras 信号通路的基因,这些变化可能与心理应激处理有关。mRNAs 和 microRNAs 的测序结果通过 qRT-PCR 和双荧光素酶报告基因检测得到验证。

结论

前额叶皮层中涉及 5-羟色胺能突触的基因下调和信号通路的失衡可能与心理应激的易感性有关。

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