Lori Adriana, Maddox Stephanie A, Sharma Sumeet, Andero Raül, Ressler Kerry J, Smith Alicia K
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
Neurobiology of Fear Laboratory, Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, United States.
Front Psychiatry. 2019 Jan 17;9:778. doi: 10.3389/fpsyt.2018.00778. eCollection 2018.
Stress and trauma profoundly influence psychiatric biobehavioral outcomes. The identification of treatment and biomarker targets would be accelerated by a broad understanding of the biological responses to these events. The goal of this study was to determine genes responsive to auditory fear conditioning (FC), a well-characterized amygdala-dependent rodent model of threat-exposure, in the presence or absence of prior stress history, providing insight into the physiological processes underlying response to trauma. RNA-sequencing was performed in blood and amygdala from mice that underwent fear conditioning with (Immo+FC) and without (FC) prior immobilization stress, a paradigm that induces HPA axis, and behavioral stress sensitization. In the amygdala, 607 genes were regulated by FC vs. home-cage (HC) controls, and 516 genes differed in stress-sensitized mice (Immo+FC vs. FC). In the former, we observed an enhancement of specific biological processes involved in learning and synaptic transmission, and in the latter processes associated with cell proliferation and the cellular response to drugs. In the blood of stress-sensitized animals, 468 genes were dynamically regulated when compared to FC, and were enriched for the biological pathways of inflammation and cytokine signaling. This study identified genes and pathways that respond to threat in the amygdala and blood of mice with and without a prior stress history and reveals the impact of stress history on subsequent inflammation. Future studies will be needed to examine the role of these dynamically regulated genes may play in human clinical stress and trauma-related disorders.
压力和创伤对精神科生物行为结果有深远影响。对这些事件的生物学反应有广泛了解将加速治疗靶点和生物标志物靶点的识别。本研究的目的是确定在有或无既往应激史的情况下，对听觉恐惧条件反射（FC）有反应的基因，FC是一种特征明确的杏仁核依赖性啮齿动物威胁暴露模型，有助于深入了解创伤反应背后的生理过程。对经历过有（固定应激+FC）和无（FC）既往固定应激的小鼠的血液和杏仁核进行RNA测序，固定应激是一种诱导下丘脑-垂体-肾上腺（HPA）轴和行为应激敏化的范式。在杏仁核中，与饲养笼（HC）对照相比，FC调节了607个基因，应激敏化小鼠（固定应激+FC与FC相比）中有516个基因不同。在前者中，我们观察到参与学习和突触传递的特定生物学过程增强，在后者中观察到与细胞增殖和细胞对药物反应相关的过程增强。在应激敏化动物的血液中，与FC相比，有468个基因受到动态调节，并且在炎症和细胞因子信号传导的生物学途径中富集。本研究确定了在有或无既往应激史的小鼠的杏仁核和血液中对威胁有反应的基因和途径，并揭示了应激史对随后炎症的影响。未来需要进一步研究这些动态调节基因在人类临床应激和创伤相关疾病中可能发挥的作用。
