Abstract：
Background: Post-Traumatic Stress Disorder (PTSD) is a severe psychological disorder characterized by intrusive thoughts, heightened arousal, avoidance, and flashbacks. Cognitive flexibility dysfunction has been linked with the emergence of PTSD, including response inhibition deficits and impaired attentional switching, which results in difficulties for PTSD patients when disengaging attention from trauma-related stimuli. However, the molecular mechanisms of cognitive flexibility deficits remain unclear. Methods: The animals were exposed to a single prolonged stress and electric foot shock (SPS&S) procedure to induce PTSD-like features. Once the model was established, the changes in cognitive flexibility were assessed using an attentional set-shifting task (ASST) in order to investigate the effects of traumatic stress on cognitive flexibility. Additionally, the molecular alterations of certain proteins (AMPA Receptor 1 (GluA1), brain-derived neurotrophic factor (BDNF), and Postsynaptic density protein 95 (PSD95) in the medial prefrontal cortex (mPFC) were measured using Western blot and immunofluorescence. Results: The SPS&S model exhibited PTSD-like behaviors and induced reversal learning and set-shifting ability deficit in the ASST. These behavioral changes are accompanied by decreased GluA1, BDNF, and PSD95 protein expression in the mPFC. Further analysis showed a correlative relationship between the behavioral and molecular alterations. Conclusions: The SPS&S model induced cognitive flexibility deficits, and the potential underlying mechanism could be mediated by GluA1-related BDNF signaling in the mPFC.
摘要：
背景：创伤后应激障碍（PTSD）是一种严重的心理障碍，其特征是侵入性思想，唤醒增强，回避,和闪回。认知灵活性功能障碍与PTSD的出现有关，包括反应抑制缺陷和注意力转换受损，这导致PTSD患者在将注意力从创伤相关刺激中脱离时遇到困难。然而,认知灵活性缺陷的分子机制尚不清楚.方法：将动物暴露于单一的长期压力和电足电击（SPS＆S）程序以诱导PTSD样特征。一旦建立了模型，为了研究创伤应激对认知灵活性的影响,我们使用注意力转移任务(ASST)评估了认知灵活性的变化.此外,某些蛋白质的分子改变（AMPA受体1（GluA1），脑源性神经营养因子(BDNF),使用蛋白质印迹和免疫荧光法测量内侧前额叶皮质（mPFC）中的突触后密度蛋白95（PSD95）。结果：SPS&S模型表现出PTSD样行为，并在ASST中引起逆转学习和集合转移能力缺陷。这些行为变化伴随着GluA1，BDNF，和PSD95蛋白在mPFC中的表达。进一步的分析表明行为和分子改变之间存在相关关系。结论：SPS&S模型诱发认知灵活性缺陷，潜在的潜在机制可能是由mPFC中GluA1相关BDNF信号介导的。
