EAGER: Estrogen Receptors and Neural Stress Circuitry

压力事件会导致身体功能和行为的短期和长期变化，从而抑制那些对即时生存不重要的功能，并促进那些对即时生存至关重要的功能。压力应对是一种重要的适应机制，使生物体能够快速适应威胁生存的挑战环境。压力影响生物体的各个器官，尤其是大脑，影响与体内平衡、认知、免疫功能、繁殖和战斗或逃跑行为反应有关的过程。有趣的是，人们观察到压力反应的性别差异，女性通常比男性对压力源表现出更高的反应。此外，也有研究表明，雌激素增强应激反应性，而雄激素抑制应激反应性。对这个项目来说，重要的是PI实验室最近的发现，雌激素对压力和焦虑的影响是由大脑中表达的雌激素受体（er - β）蛋白介导的。目前的假设是，在不同的大脑区域内，er - β的激活对于调节应激反应至关重要，应激反应随后会影响整个身体的应激回路。这个EAGER项目将创建一个独特的模型，在这个模型中，蛋白质er - β可以在特定的细胞类型和/或在选定的时间在大脑的目标区域中被操纵，同时仍然允许在其他组织中表达这种关键的信号蛋白。该模型系统将被用于研究er - β在产生压力反应性性别差异中的作用，不仅在大脑中，而且还可以更好地理解压力如何在一般生理和行为水平上影响生物体。这些发现不仅会影响神经内分泌对压力的调节，还会影响发育生物学、生殖生物学、认知神经科学和性别差异进化等领域。该项目将为混合领域的学生和研究员提供培训经验，该领域将使用综合方法和独特的模型系统将分子技术与生理学相结合。目标是让学员参与科学研究的各个方面，包括分子生物学和基因组学的先进技术方法、数据解释和分析、研究伦理、在国家会议上展示数据以及发表他们的发现。

Stressful events cause short- and long-term changes in body functions and behavior to suppress those that are not critical for immediate survival and promote those that are. Stress coping is an important adaptive mechanism in allowing the organism to quickly adapt to challenging circumstances that threaten survival. Stress influences various organs of organisms, including especially the brain, to affect processes related to homeostasis, cognition, immune function, reproduction, and fight-or-flight behavioral responses. Interestingly, sex differences in stress reactivity have been observed, with females usually exhibiting higher reactivity to a stressor than males. Furthermore, it has also been demonstrated that estrogens enhance stress reactivity while androgens inhibit it. Important to this project are recent findings from the PI's laboratory that estrogen effects on stress and anxiety are mediated by the protein estrogen receptor beta (ER-beta) expressed in the brain. The working hypothesis is that activation of ER-beta within distinct brain regions is critical for modulation of stress-reactivity, which then impacts the stress circuitry throughout the body. This EAGER project will create a unique model in which the protein ER-beta can be manipulated in a specific cell type and/or at a chosen time in targeted regions of the brain while still allowing the expression of this key signaling protein in other tissues. This model system will be utilized to study the role of ER-beta in producing sex differences in stress reactivity not only in the brain, but also to better understand how stress affects the organism at the general physiological and behavioral levels. The findings will impact not only understanding of the neuroendocrine regulation of stress, but also the areas of developmental biology, reproductive biology, cognitive neuroscience, and the evolution of sex differences. The project will provide training experience for students and fellows in a hybrid area that integrates molecular techniques with physiology using a comprehensive approach and unique model systems. The goal is to involve the trainees in all aspects of scientific research including advanced technical approaches in molecular biology and genomics, data interpretation and analysis, research ethics, presentation of data at national meetings, and publication of their findings.