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成年老鼠目睹应激事件后的神经生物学后遗症。

Neurobiological sequelae of witnessing stressful events in adult mice.

机构信息

Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL, USA.

出版信息

Biol Psychiatry. 2013 Jan 1;73(1):7-14. doi: 10.1016/j.biopsych.2012.06.006. Epub 2012 Jul 12.

Abstract

BACKGROUND

It is well known that exposure to severe stress increases the risk for developing mood disorders. However, most chronic stress models in rodents involve at least some form of physically experiencing traumatic events.

METHODS

This study assessed the effects of a novel social stress paradigm that is insulated from the effects of physical stress. Specifically, adult male C57BL/6J mice were exposed to either emotional (ES) or physical stress (PS) for 10 minutes per day for 10 days. The ES mice were exposed to the social defeat of a PS mouse by a larger, more aggressive CD-1 mouse from the safety of an adjacent compartment.

RESULTS

Like PS mice, ES mice exhibited a range of depression- and anxiety-like behaviors both 24 hours and 1 month after the stress. Increased levels of serum corticosterone, part of the stress response, accompanied these behavioral deficits. Based on previous work that implicated gene expression changes in the ventral tegmental area (a key brain reward region) in the PS phenotype, we compared genome-wide mRNA expression patterns in this brain region of ES and PS mice using RNA-seq. We found significant overlap between these conditions, which suggests several potential gene targets for mediating the behavioral abnormalities observed.

CONCLUSIONS

These findings demonstrate that witnessing traumatic events is a potent stress in adult male mice capable of inducing long-lasting neurobiological perturbations.

摘要

背景

众所周知,暴露于严重的压力会增加患情绪障碍的风险。然而,大多数啮齿动物的慢性应激模型至少涉及某种形式的身体创伤体验。

方法

本研究评估了一种新型社会应激范式的影响,该范式不受身体应激影响。具体来说,成年雄性 C57BL/6J 小鼠每天接受 10 分钟的情绪(ES)或身体应激(PS),共 10 天。ES 小鼠在安全的相邻隔室中,通过来自更大、更具攻击性的 CD-1 小鼠的社交挫败来暴露于 PS 小鼠的压力下。

结果

与 PS 小鼠一样,ES 小鼠在应激后 24 小时和 1 个月均表现出一系列抑郁和焦虑样行为。应激反应的一部分血清皮质酮水平升高伴随着这些行为缺陷。基于先前的工作表明,腹侧被盖区(大脑奖励区域的关键部位)中的基因表达变化与 PS 表型有关,我们使用 RNA-seq 比较了 ES 和 PS 小鼠该脑区的全基因组 mRNA 表达模式。我们发现这些条件之间存在显著重叠,这表明有几个潜在的基因靶点可以介导观察到的行为异常。

结论

这些发现表明,目睹创伤事件是成年雄性小鼠的一种强烈应激,能够引起持久的神经生物学改变。

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