CRH RECEPTORS AND AVP IN ACUTE AND CHRONIC STRESS

下丘脑-垂体-肾上腺轴是应激系统的重要组成部分，它使人类和其他生物能够对感知到的环境威胁做出反应。 该系统最重要的调节因子是促肾上腺皮质激素释放激素（CRH）和加压素（AVP）。HPA轴的失调与几种慢性疾病有关，如抑郁症、神经性厌食症、肥胖症、酒精中毒、纤维肌痛和慢性焦虑状态。 针对这些疾病的药物的开发正在进行中，尽管慢性阻断CRH受体和代偿机制的发展的影响尚不清楚。 该项目的总体目标是使用CRH缺陷小鼠模型，帮助描述CRH和AVP在调节应激反应中的各自作用。 第一个具体的目标将测试的假设，CRH的释放，引起的压力，下调自己的反应和上调AVP的反应下丘脑神经元。 将在经历急性和慢性应激范例的CRH缺陷小鼠和正常小鼠中检查下丘脑中CRH、AVP和CRH受体表达的变化。 第二个具体目标涉及c-fos表达的检测，其已被用作脑的应激相关区域的神经元激活的标记。 通过研究CRH缺陷小鼠和正常小鼠c-fos表达的差异，将探讨CRH在适应慢性应激中的可能作用。

The hypothalamic-pituitary-adrenal HPA) axis is an important component of the stress system, which enables humans and other organisms to respond to perceived environmental threats. The most important regulators of this system are corticotropin-releasing hormone (CRH) and vasopressin (AVP). Dysregulation of the HPA axis is implicated in several chronic diseases such as depression, anorexia nervosa, obesity, alcoholism, fibromyalgia, and chronic anxiety states. The development of drugs for these disorders targeting CRH receptors is underway, though the effects of chronically blocking CRH receptors and of the development of compensatory mechanisms are unknown. The overall goal of the proposed project is to help delineate the respective roles of CRH and AVP in modulating the stress response, using the CRH deficient mouse model. The first specific aim will test the hypothesis that CRH release, brought on by stress, down-regulates its own response and upregulates the response of AVP in hypothalamic neurons. Changes in CRH, AVP, and CRH receptor expression in the hypothalamus will be examined in CRH-deficient and normal mice subjected to acute and chronic stress paradigms. The second specific aim involves the detection of c-fos expression, which has been used as a marker for neuronal activation of stress-related areas of the brain. By studying differences in c-fos expression in CRH-deficient and normal mice, the possible role of CRH in adaptation to chronic stress will be explored.