Collaborative Research: Novel Corticosteroid Actions on Neurotransmitter Function

当生物体暴露在广泛的应激源中时，神经内分泌级联反应会导致应激激素(皮质类固醇)释放到血液中。皮质类固醇会导致生理和大脑功能的变化，这对处理紧急情况至关重要，但持续的皮质类固醇升高会产生众所周知的压力有害影响。所有脊椎动物都需要快速和强大的应激反应，以及终止这种反应的有效手段。终止这种反应的大脑机制仍然知之甚少。这些研究探索了一种新的机制，通过这种机制，应激激素可以提供负反馈来终止应激反应。亚利桑那州立大学、科罗拉多大学和南达科他大学将进行合作实验，以测试这一假设，即在导致负反馈和相关行为变化的压力反应中，皮质类固醇会阻止神经递质5-羟色胺在特定大脑区域的清除。最新的神经化学、脑成像和行为研究将确定皮质类固醇是否通过新描述的大脑转运体阻止5-羟色胺的运输，导致5-羟色胺信号增强和应激反应抑制。这些研究还将用于培训学生(研究生、本科生和高中)和博士后研究人员进行尖端神经科学研究。原则调查员(PI)提供的研究培训对于鼓励年轻学生欣赏科学推理和从事科学事业非常重要。合共资助了100多项来自不同背景的学生的本科生研究项目，而每一位私人督学也有致力于研究生教育和研究的长期记录。通过这些研究，每个PI将继续作出明确的努力，接触到经济上处于不利地位或代表性不足的群体。

When an organism is exposed to a wide range of stressors, a neuroendocrine cascade leads to the release of stress hormones (corticosteroids) into the bloodstream. The corticosteroids produce changes in physiology and brain function that are crucial for dealing with emergencies, but persistent elevation of corticosteroids produce the well known deleterious effects of stress. All vertebrates need a rapid and robust stress response as well as an effective means of terminating this response. The brain mechanisms that terminate this response remain poorly understood. These studies investigate a novel mechanism through which stress hormones could provide negative feedback to terminate the stress response. Collaborative experiments will be conducted at Arizona State University, University of Colorado and University of South Dakota to test the hypothesis that corticosteroids block clearance of the neurotransmitter serotonin in specific brain regions during a stress response leading to negative feedback and associated changes in behavior. State-of-the-art neurochemical, brain imaging and behavioral studies will determine whether corticosteroids block serotonin transport via a newly described transporter in brain, leading to enhanced serotonin signaling and suppression of the stress response. These studies will also serve to train students (graduate, undergraduate, and high school) and post-doctoral researchers in cutting-edge neuroscience research. The research training provided by the principle investigators (PIs) is important for encouraging young students to appreciate scientific reasoning and pursue careers in science. Collectively, the PIs have sponsored over 100 undergraduate research projects from students with diverse backgrounds, and each of the PIs also has a long track record of dedication to graduate student education and research. With these studies, each PI will continue to make explicit efforts to reach out to economically disadvantaged or underrepresented groups.