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PNAS:预测创伤后应激障碍的生物标志物

  1. 创伤后应激障碍
  2. 生物标志物

来源:生物谷 2014-08-17 20:55

根据刊登在PNAS杂志上的一项大鼠研究提示:应激激素--糖皮质激素针对性靶向的基因的血液表达水平,可以是一个物理措施治疗创伤后应激障碍(PTSD)或生物标志物预测PTSD。

2014年8月14日讯 /生物谷BIOON/--根据刊登在PNAS杂志上的一项大鼠研究提示:血液中应激激素--糖皮质激素的表达水平,是预测PTSD的潜在生物标志物。

这也使得甾体激素的受体--糖皮质激素受体,成为新的潜在药物靶标。创伤后应激障碍(PTSD)症状可能包括痛苦回忆的重现,梦魇和严重焦虑等。不是每个人在经历创伤后都会出现创伤后应激障碍,这也就是为什么要进行该项研究,旨在确定生物标志物,可以更好地衡量每个人发生障碍的可能性。

首席研究员Rachel Yehuda博士表示:研究目标是确定哪些基因的差异表达与创伤后应激障碍有关。我们发现,创伤后应激障碍动物与对创伤适应性强的动物相比,有很多基因和信号途径是不同的,并且不同的基因和信号途径都与糖皮质激素受体相关,这表明我们几乎已经确定潜在治疗创伤后应激障碍的治疗靶标。

该研究小组将一组雄性和雌性大鼠暴露于被猫尿弄脏的垃圾环境下,这一掠夺性气味模仿危及生命的情况。到现在,大多数的创伤后应激障碍研究只用雄性大鼠进行研究。但现在,研究人员将雌性大鼠也纳入这项研究中,因为女性比男性对于发生创伤后应激障碍显得更为脆弱。

基于大鼠暴露于被猫尿弄脏的垃圾环境后的行为,对大鼠进行分类。研究人员还研究了这些大鼠的血液和胁迫应答大脑区域的基因表达模式。暴露于被猫尿污染的垃圾环境下10分钟,一周之后,与适应性强的老鼠相比,有些大鼠表现出较高的焦虑和过度反应,并且大鼠体内所有组织中表现出糖皮质激素受体信号传导的改变。

此外,暴露于猫尿气味后,一些大鼠用一种激素--皮质酮(激活糖皮质激素受体)进行治疗。与未治疗大鼠相比,治疗老鼠一个星期后所表现出的焦虑和兴奋水平较低。(生物谷Bioon.com)

Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes

Nikolaos P. Daskalakis, Hagit Cohen, Guiqing Cai, Joseph D. Buxbaum, and Rachel Yehuda.

Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., “PTSD-like”) and resilient (i.e., minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (4–21%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factors were first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associated with individual differences when using the most stringent statistical threshold. Corticosterone treatment 1 h after PSS-exposure prevented anxiety and hyperarousal 7 d later in both sexes, confirming the GR involvement in the PSS behavioral response. In conclusion, genes and pathways associated with extreme differences in the traumatic stress behavioral response can be distinguished from those associated with trauma exposure. Blood-based biomarkers can predict aspects of brain signaling. GR signaling is a convergent signaling pathway, associated with trauma-related individual differences in both sexes.

 

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