Ding Jinlan, Chen Xinzhao, Han Fang, Meijer Onno C
Division of Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden University, Leiden, Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden University, Leiden, Netherlands.
Front Behav Neurosci. 2021 Nov 17;15:756903. doi: 10.3389/fnbeh.2021.756903. eCollection 2021.
Stress-related neuropsychiatric disorders are often accompanied by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. In patients suffering from post-traumatic stress disorder (PTSD), increased sensitivity of glucocorticoid negative feedback has regularly been observed. The single prolonged stress (SPS) paradigm was developed to model increased negative feedback and other aspects of PTSD in rats. In this study, we used a setup that precluded the evaluation of negative feedback but rather served to test the hypothesis of the enhanced glucocorticoid receptor (GR) signaling in higher brain areas. We injected corticosterone or vehicle 7 days after SPS and evaluated plasma corticosterone, as well as gene expression in the dorsal hippocampus and amygdala. We observed a strikingly rapid change in the expression of established GR target genes ( = 30 min) only in the SPS group on exogenous corticosterone injection. Our results extend the notion of increased GR sensitivity in PTSD to include transcriptional responses in the hippocampus.
与应激相关的神经精神疾病常伴有下丘脑-垂体-肾上腺（HPA）轴功能障碍。在创伤后应激障碍（PTSD）患者中，经常观察到糖皮质激素负反馈敏感性增加。单次长时间应激（SPS）范式被开发用于模拟大鼠中负反馈增加及PTSD的其他方面。在本研究中，我们使用了一种装置，该装置无法评估负反馈，而是用于检验高等脑区糖皮质激素受体（GR）信号增强的假说。我们在SPS后7天注射皮质酮或赋形剂，并评估血浆皮质酮以及背侧海马体和杏仁核中的基因表达。我们观察到，仅在SPS组中，在外源性皮质酮注射后，既定GR靶基因的表达出现了惊人的快速变化（=30分钟）。我们的结果扩展了PTSD中GR敏感性增加的概念，以包括海马体中的转录反应。
