Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder
Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder
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DOI：
10.1016/j.nbd.2016.01.012
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发表时间：
2016-04-01
影响因子：
6.1
通讯作者：
Richter-Levin, Gal
中科院分区：
文献类型：
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作者：
Ardi, Ziv;Albrecht, Anne;Richter-Levin, Gal
人类精神疾病的诊断是基于将个体与正常人群进行比较。然而，许多动物模型分析平均群体效应，从而损害了它们的翻译能力。这种差异在创伤后应激障碍（PTSD）中尤其相关，其中只有少数人在创伤经历后发展出这种障碍。我们利用一种新的行为分析方法，可以在创伤暴露人群中对受影响和未受影响的个体进行分类。四周后，将其在旷场和高架十字迷宫中的个体表现与对照组进行比较，行为分析显示，只有一部分暴露于UWT的大鼠发育出长时间的，持续的行为症状幼年应激是PTSD的一个危险因素，通过预先暴露于应激状态，PTSD大鼠的患病率进一步增加。为了验证这一概念，我们分析了腹侧、背侧海马和基底外侧杏仁核中GABAA受体亚单位α 1和α 2的表达水平。在暴露动物的腹侧海马体中观察到主要是al的表达增加，但在背侧海马体中没有观察到，这在传统上被解释为与应激导致的精神病理学相关。然而，行为分析显示，这种增加的表达仅限于暴露未受影响的个体，这表明与毒性相关的表达调节。这些结果为在PTSD动物模型中采用行为分析的重要性提供了证据，以便更好地了解压力脆弱性和弹性的神经基础。(C)2016 Elsevier Inc. All rights reserved.
Diagnosis of psychiatric disorders in humans is based on comparing individuals to the normal population. However, many animal models analyze averaged group effects, thus compromising their translational power. This discrepancy is particularly relevant in posttraumatic stress disorder (PTSD), where only a minority develop the disorder following a traumatic experience.In our PTSD rat model, we utilize a novel behavioral profiling approach that allows the classification of affected and unaffected individuals in a trauma-exposed population.Rats were exposed to underwater trauma (UWT) and four weeks later their individual performances in the open field and elevated plus maze were compared to those of the control group, allowing the identification of affected and resilient UWT-exposed rats.Behavioral profiling revealed that only a subset of the UWT-exposed rats developed long-lasting behavioral symptoms. The proportion of affected rats was further enhanced by pre-exposure to juvenile stress, a well described risk factor of PTSD.For a biochemical proof of concept we analyzed the expression levels of the GABAA receptor subunits alpha l and alpha 2 in the ventral, dorsal hippocampus and basolateral amygdala. Increased expression, mainly of al, was observed in ventral but not dorsal hippocampus of exposed animals, which would traditionally be interpreted as being associated with the exposure-resultant psychopathology. However, behavioral profiling revealed that this increased expression was confined to exposed-unaffected individuals, suggesting a resilience-associated expression regulation. The results provide evidence for the importance of employing behavioral profiling in animal models of PTSD, in order to better understand the neural basis of stress vulnerability and resilience. (C) 2016 Elsevier Inc. All rights reserved.