Huang Gengdi, Iqbal Javed, Shen Dan, Xue Yan-Xue, Yang Mei, Jia Xiaojian
State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China.
Department of Addiction Medicine, Shenzhen Engineering Research Center for Precision Psychiatric Technology, Shenzhen Clinical Research Center for Mental Disorders, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, China.
Front Psychiatry. 2023 Aug 24;14:1247714. doi: 10.3389/fpsyt.2023.1247714. eCollection 2023.
The experience of traumatic stress can engender lasting memories associated with the trauma, often resulting in post-traumatic stress disorder (PTSD). However, only a minority of individuals develop PTSD symptoms upon exposure. The neurobiological mechanisms underlying the pathology of PTSD are poorly understood. Utilizing a rat model of PTSD, the Single Prolonged Stress (SPS) paradigm, we were able to differentiate between resilient and susceptible individuals. Fourteen days after the SPS exposure, we conducted the behavioral analyses using Elevated Plus Maze (EPM) and Open Field (OF) tests to identify male rats as trauma resilient or susceptible. We focused on the microRNA (miRNA) profiles of the infralimbic (IL) and prelimbic (PL) cortical regions, known to be crucial in regulating the stress response. Our investigation of stressed rats exposed to the SPS procedure yielded divergent response, and differential expression microRNAs (DEmiRs) analysis indicated significant differences in the IL and PL transcriptional response. In the IL cortex, the GO analysis revealed enriched GO terms in the resilient versus control comparison, specifically related to mitogen-activated protein kinase and MAP kinase signaling pathways for their molecular functions as well as cytosol and nucleoplasm for the biological process. In the susceptible versus resilient comparison, the changes in molecular functions were only manifested in the functions of regulation of transcription involved in the G1/S transition of the mitotic cell cycle and skeletal muscle satellite cell activation. However, no enriched GO terms were found in the susceptible versus control comparison. In the PL cortex, results indicated that the DEmiRs were enriched exclusively in the cellular component level of the endoplasmic reticulum lumen in the comparison between resilient and control rats. Overall, our study utilized an animal model of PTSD to investigate the potential correlation between stress-induced behavioral dysfunction and variations in miRNA expression. The aforementioned discoveries have the potential to pave the way for novel therapeutic approaches for PTSD, which could involve the targeted regulation of transcriptome expression.
创伤应激经历可产生与创伤相关的持久记忆，常导致创伤后应激障碍（PTSD）。然而，只有少数个体在暴露于创伤后会出现PTSD症状。PTSD病理背后的神经生物学机制尚不清楚。利用PTSD大鼠模型，即单次长时间应激（SPS）范式，我们能够区分有恢复力和易感性的个体。在SPS暴露14天后，我们使用高架十字迷宫（EPM）和旷场（OF）试验进行行为分析，以确定雄性大鼠是创伤恢复力强还是易感性强。我们关注了已知在调节应激反应中起关键作用的边缘下（IL）和边缘前（PL）皮质区域的微小RNA（miRNA）谱。我们对接受SPS程序的应激大鼠的研究产生了不同的反应，差异表达微小RNA（DEmiRs）分析表明IL和PL转录反应存在显著差异。在IL皮质中，基因本体（GO）分析显示，在恢复力强的大鼠与对照大鼠的比较中，GO术语富集，具体涉及丝裂原活化蛋白激酶和MAP激酶信号通路的分子功能，以及生物过程中的细胞质和核质。在易感性大鼠与恢复力强的大鼠的比较中，分子功能的变化仅表现在有丝分裂细胞周期G1/S转换和骨骼肌卫星细胞激活所涉及的转录调节功能上。然而，在易感性大鼠与对照大鼠的比较中未发现富集的GO术语。在PL皮质中，结果表明，在恢复力强的大鼠与对照大鼠的比较中，DEmiRs仅在内质网腔的细胞成分水平上富集。总体而言，我们的研究利用PTSD动物模型来研究应激诱导的行为功能障碍与miRNA表达变化之间的潜在相关性。上述发现有可能为PTSD的新型治疗方法铺平道路，这可能涉及转录组表达的靶向调节。
