Role of corticosterone in altered neurobehavioral responses to acute stress in a model of compromised hypothalamic-pituitary-adrenal axis function.
Role of corticosterone in altered neurobehavioral responses to acute stress in a model of compromised hypothalamic-pituitary-adrenal axis function.
复制标题
DOI：
10.1016/j.psyneuen.2018.12.010
复制
发表时间：
2019-04
影响因子：
3.7
通讯作者：
Karatsoreos IN
中科院分区：
文献类型：
--
作者：
Kinlein SA;Phillips DJ;Keller CR;Karatsoreos IN
生物体应对应激经历的能力取决于其适当参与中枢和外周系统(如下丘脑-垂体-肾上腺(HPA)轴)以适应不断变化的环境需求的能力。HPA轴是神经和行为应激反应的主要神经内分泌介质，该系统的功能障碍与患精神健康障碍(如抑郁、焦虑和创伤后应激障碍)的风险增加有关。然而，HPA功能失调导致对应激的异常行为反应的机制尚不清楚。在这里，我们测试了皮质酮(Cort)诱导的HPA轴破坏如何影响雄性C57BL/6N小鼠对应激的行为反应，并探讨了这些行为在大脑中的相关性。我们发现，在旷场实验中，慢性HPA干扰可钝化急性应激诱导的梳理和养育行为，这种影响伴随着下丘脑室旁核(PVH)和丘脑室旁核(PVT)FOS免疫反应的降低。急性应激前注射美托拉酮阻断皮质醇的分泌不能概括慢性HPA干扰对旷场行为的影响，急性皮质醇替代不能挽救慢性HPA干扰后的正常行为应激反应。这表明，在急性情况下，CORT不是这些正常反应所必需的，也不足以挽救慢性HPA调节失调的缺陷。总而言之，这些发现支持了慢性HPA失调导致与压力相关的大脑回路适应的假设，并证明这些变化可以影响有机体对压力暴露的行为反应。
An organism’s capacity to cope with stressful experiences is dependent on its ability to appropriately engage central and peripheral systems, such as the hypothalamic-pituitary-adrenal (HPA) axis, to adapt to changing environmental demands. The HPA axis is a primary neuroendocrine mediator of neural and behavioral responses to stress, and dysfunction of this system is linked to increased risk for developing mental health disorders such as depression, anxiety, and post-traumatic stress disorder. However, the mechanisms by which dysregulated HPA function results in abnormal behavioral responses to stress are poorly understood. Here, we tested how corticosterone (CORT)-induced HPA axis disruption affects behavioral responses to stress in male C57BL/6N mice, and probed correlates of these behaviors in the brain. We show that chronic HPA disruption blunts acute stress-induced grooming and rearing behaviors in the open field test, effects which were accompanied by decreased FOS immunoreactivity in the paraventricular nucleus of the hypothalamus (PVH) and paraventricular nucleus of the thalamus (PVT). Blockade of CORT secretion with metyrapone injection prior to acute stress did not recapitulate the effects of chronic HPA disruption on open field behavior, and acute CORT replacement did not rescue normal behavioral stress responses following chronic HPA disruption. This suggests that under acute conditions, CORT is not necessary for these responses normally, nor sufficient to rescue the deficits of chronic HPA dysregulation. Together, these findings support the hypothesis that chronic HPA dysregulation causes adaptation in stress-related brain circuits and demonstrate that these changes can influence an organism’s behavioral response to stress exposure.
登录
查看更多内容
影响因子：
3.2
作者：
Evanson NK;Herman JP;Sakai RR;Krause EG
通讯作者：
Krause EG
丘脑室旁核微量注射食欲素引起的情绪行为变化
影响因子：
3.6
作者：
Li, Yonghui;Li, Sa;Kirouac, Gilbert J.
通讯作者：
Kirouac, Gilbert J.
影响因子：
4.8
作者：
Heydendael, Willem;Sharma, Kanika;Bhatnagar, Seema
通讯作者：
Bhatnagar, Seema
DOI：
10.1038/nrn.2015.8
发表时间：
2016-01
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Kalueff AV;Stewart AM;Song C;Berridge KC;Graybiel AM;Fentress JC
通讯作者：
Fentress JC
影响因子：
3
作者：
Hsu DT;Kirouac GJ;Zubieta JK;Bhatnagar S
通讯作者：
Bhatnagar S