Cellular Mechanisms Mediating Acute Stress Hormone Action in Brain

介导大脑中急性应激激素作用的细胞机制

• 批准号: 0220473
• 负责人: Miles Orchinik
• 金额: $ 36.49万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0220473&HistoricalAwards=false
• 关键词: Cellular; Mechanisms; Mediating; Acute; Stress

Glucocorticoids, such as corticosterone (CORT), are an important group of steroid hormones that modulate cellular and behavioral responses to stress. Their action can involve genomic mechanisms in the cell nucleus, and also much faster non-genomic actions involving receptors on the cell membrane. The cellular mechanisms mediating responses to acute, as distinct from chronic, stress are still not well understood. Recent evidence suggests that CORT interactions with behaviorally important peptide hormones, in particular arginine vasotocin (AVT), are critical during acute stress. This project examines how CORT and AVT interact within brain cells in response to acute stress, using the salamander as a novel and accessible system to combine biochemistry with behavior. The interactions of the hormones in triggering intracellular biochemical signaling pathways will be tested in specific contexts, in terms of behavior and neuroendocrine state. Results will be important for understanding fundamental cellular mechanisms of stress hormone action in vertebrates. The impact will extend beyond neuroendocrinology to endocrinology and stress-related behavior, as well as cell biology related to signaling. Valuable training of students at several levels in this productive laboratory also will continue to include students with handicaps and those from underrepresented groups.

糖皮质激素，如皮质酮（CORT），是一组重要的类固醇激素，可调节细胞和行为对压力的反应。它们的作用可以涉及细胞核中的基因组机制，也可以涉及细胞膜上受体的更快的非基因组作用。细胞机制介导的反应急性，不同于慢性，压力仍然没有很好地理解。最近的证据表明，CORT与行为重要的肽激素，特别是精氨酸缩宫素（AVT）的相互作用在急性应激期间是至关重要的。该项目研究了CORT和AVT如何在脑细胞内相互作用，以应对急性应激，使用蝾螈作为一个新的和可接近的系统，将生物化学与行为结合起来。激素在触发细胞内生化信号通路中的相互作用将在特定的环境中进行测试，在行为和神经内分泌状态方面。研究结果对于理解应激激素在脊椎动物中作用的基本细胞机制具有重要意义。其影响将从神经内分泌学扩展到内分泌学和压力相关行为，以及与信号传导相关的细胞生物学。在这个富有成效的实验室中，对学生在几个层次上的宝贵培训也将继续包括残疾学生和来自代表性不足群体的学生。