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心理社会应激后孕鼠中 microRNA-206-3p 和 BDNF 表达与焦虑相关行为的关系

Anxiety-Related Behaviours Associated with microRNA-206-3p and BDNF Expression in Pregnant Female Mice Following Psychological Social Stress.

机构信息

Beijing Institutes of Life Science, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.

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

出版信息

Mol Neurobiol. 2018 Feb;55(2):1097-1111. doi: 10.1007/s12035-016-0378-1. Epub 2017 Jan 14.

Abstract

Stress during pregnancy can induce various psychological disorders in women. However, the association linking psychological stress during pregnancy with abnormal behaviours in females remains largely unknown. We employed a novel psychological stress model by introducing pregnant mice to witness the defeat process of their mated partner (WDPMP) and examined the effects of WDPMP on depression-/anxiety-like behaviours and on the expression of brain-derived neurotrophic factor (BDNF) and miR-206-3p in the hippocampus, medial prefrontal cortex (mPFC) and amygdala. Compared to pregnant control (PC) mice, pregnant stressed (PS) mice showed decreased sucrose preference during the late period of gestation, and after lactation, they spent less time in the open arms of the elevated plus maze and in the light chamber of the light/dark box. After lactation, decreased BDNF expression in both the hippocampus and mPFC of PS mice was found to be associated with enhanced miR-206-3p levels; meanwhile, elevated BDNF associated with decreased miR-206-3p expression was evident in the amygdala of the same PS mice. DNA methylation level in the Bdnf promoter did not show difference between PC and PS mice in the hippocampus. Transfection of miR-206-3p resulted in decreased BDNF levels in vitro. These results suggest that WDPMP stress during gestation can induce long-term mood alterations in pregnant mice, which may correlate with changes in miR-206-3p and BDNF expression in the hippocampus, mPFC and amygdala.

摘要

怀孕期间的压力会导致女性出现各种心理障碍。然而,孕妇心理压力与女性异常行为之间的联系在很大程度上仍不清楚。我们采用了一种新的心理应激模型,即将怀孕的老鼠暴露于观察其配偶失败的过程(WDPMP)中,并研究了 WDPMP 对抑郁/焦虑样行为的影响,以及对海马体、内侧前额叶皮质(mPFC)和杏仁核中脑源性神经营养因子(BDNF)和 miR-206-3p 表达的影响。与怀孕对照组(PC)相比,怀孕应激组(PS)在妊娠晚期表现出蔗糖偏好降低,产后它们在高架十字迷宫的开放臂和明暗箱的亮室中停留的时间更少。产后,PS 组的海马体和 mPFC 中 BDNF 表达减少与 miR-206-3p 水平升高有关;同时,在同一 PS 组的杏仁核中也发现了 BDNF 升高与 miR-206-3p 表达降低相关。PC 和 PS 组在海马体中 Bdnf 启动子的 DNA 甲基化水平没有差异。miR-206-3p 的转染导致体外 BDNF 水平降低。这些结果表明,孕期 WDPMP 应激可引起怀孕小鼠长期情绪改变,这可能与海马体、mPFC 和杏仁核中 miR-206-3p 和 BDNF 表达的变化有关。

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