Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD
Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD
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DOI：
10.1016/j.euroneuro.2015.02.004
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发表时间：
2015-06-01
影响因子：
5.6
通讯作者：
Cohen, Hagit
中科院分区：
文献类型：
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作者：
Fenchel, Daphna;Levkovitz, Yechiel;Cohen, Hagit
下丘脑-垂体-肾上腺（HPA）轴在应激反应中起主要作用，下丘脑-垂体-性腺（HPG）轴与抑制对方的能力密切相关。Texine是HPG的一种产品，除了作为性激素的功能外，还具有许多有益的作用，包括抗焦虑特性。在这项研究中，我们研究了应激暴露对性腺激素的影响，以及它们在PTSD动物模型中调节焦虑样反应的功效。雄性大鼠暴露于捕食者气味应激，随后分析脑雄激素受体（AR）受体和雌激素受体α（ER α）的表达。使用高架十字迷宫、声惊吓反应和创伤提示反应评价睾酮、睾酮受体拮抗剂（氟米特）或溶剂立即处理的行为效应。治疗后还测量了循环皮质酮和睾酮的水平。以同样的方式探索延迟睾酮治疗的行为效应。我们报告说，动物的行为是非常混乱的（EBR）选择性地显示显着下调AR和ER α在美洲狮。立即用氟磺酰脲治疗或延迟用睾酮治疗显著增加了最小行为反应（MBR）的患病率，降低了EBR的患病率，并获得了良好的行为结果。对照组未接触动物的睾酮水平较高，而对照组接触动物的皮质酮水平较高。这项研究表明，性腺类固醇激素参与捕食者气味应激的神经生物学反应，因此值得进一步研究作为一个潜在的治疗途径，用于治疗焦虑相关疾病。(C)2015 Elsevier B. V.和ECNR保留所有权利。
The hypothalamic-pituitary-adrenal (HPA) axis, which plays a major role in the response to stress, and the hypothalamic-pituitary-gonadal (HPG) axis are closely linked with the ability to inhibit the other. Testosterone, a product of the HPG, has many beneficial effects beyond its functions as a sex hormone including anti-anxiety properties. In this study we examined the effect of stress exposure on gonadal hormones, and their efficacy in modulating anxiety-like response in an animal model of PTSD. Male rats were exposed to predator scent stress, followed by analysis of brain expression of androgen receptor (AR) receptor and estrogen receptor a (ER alpha). The behavioral effects of immediate treatment with testosterone, testosterone receptor antagonist (fiutamide) or vehicle were evaluated using the elevated plus-maze, acoustic startle response and trauma-cue response. Levels of circulating corticosterone and testosterone were also measured after treatment. The behavioral effects of delayed testosterone treatment were explored in the same manner. We report that animals whose behavior was extremely disrupted (EBR) selectively displayed significant down-regulation of AR and ERa in the hippocannpus. Immediate treatment with fiutamide or delayed treatment with testosterone significantly increased prevalence rates of minimal behavioral response (MBR) and decreased prevalence of EBR with favorable behavioral results. Testosterone levels were higher in control un-exposed animals, while corticosterone was higher in control exposed animals. This study suggests that gonadal steroid hormones are involved in the neurobiological response to predator scent stress and thus warrant further study as a potential therapeutic avenue for the treatment of anxiety-related disorders. (C) 2015 Elsevier B.V. and ECNR All rights reserved.