Corticosteroid Dependent Mechanisms of Stress Adaptation

皮质类固醇依赖性压力适应机制

• 批准号: 6941241
• 负责人: ROBERT L SPENCER
• 金额: $ 10.36万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6941241
• 关键词: behavioral /social science research tag; behavioral habituation /sensitization; corticosteroid receptors; corticosteroids; corticotropin releasing factor; gene expression; hippocampus; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; immunocytochemistry; laboratory rat; microinjections; psychological adaptation; receptor expression; stress

DESCRIPTION (provided by applicant): This is an application for an Independent Scientist Award (K02) that would be essential in allowing the PI to devote at least 75 percent of his effort to his research program and research career development. For the past 6 years the PI has systematically studied a stress habituation paradigm in rats and found that the expression of habituation depended on corticosteroid negative feedback, especially as a result of corticosteroid actions mediated by mineralocorticoid receptors (MR). This work was primarily supported by NIH B-Start (MH54742) and R29 (DK49143) awards. Recently, the PI has been awarded a 5-year R01 award (MH62456) to pursue further these studies. The funded research project entails an extensive range of studies that will 1) determine the brain regions critical to MR-mediated modulation of stress habituation, 2) characterization of CRH and AVP gene expression and modulation with habituation and altered corticosteroid negative feedback, 3) examination of the extent to which HPA axis stress habituation is associated with a generalized shift in MR-mediated corticosteroid negative feedback, and 4) determine if HPA axis stress habituation is associated with changes in corticosteroid receptor expression. The PI's immediate career objectives are to extend his research program in terms of its quality, productivity and breadth of technical expertise. The PI's long-term career objective is to make a substantial scientific contribution to the understanding of the neural adaptive processes that impact on stress responses. A Career Development Plan is proposed that will be instrumental in helping the PI achieve these career objectives by extending the PI's collaborations and training in the areas of neuroanatomy, cell biology, molecular biology, and systems physiology. Increased knowledge, technical expertise and interaction with specialists in each of these areas will be vital for ongoing and future studies in the PI's laboratory designed to decisively determine underlying mechanisms of stress adaptation. The PI's Department and Institution are committed to supporting the PI's research program and have provided extensive laboratory space and physical resources. Through Department approved teaching reduction, the K02 award will increase substantially the amount of time and coherent blocks of time that the PI can devote to his research and career development, thereby assuring the success of these endeavors.

描述（由申请人提供）：这是一个独立科学家奖（K02）的申请，这对于允许PI至少将其努力的75％努力用于他的研究计划和研究职业发展至关重要。在过去的6年中，PI系统地研究了大鼠的应力习惯范式，发现习惯的表达取决于皮质类固醇的负反馈，尤其是由于矿物皮质激素受体介导的皮质类固醇作用（MR）。这项工作主要得到NIH B-Start（MH54742）和R29（DK49143）奖项的支持。最近，PI获得了5年R01奖（MH62456），以进一步进行这些研究。资助的研究项目需要进行广泛的研究，以1）确定对MR介导的压力习惯的调节至关重要的大脑区域，2）CRH和AVP基因表达的表征和AVP基因表达和与习惯性的调节以及皮质类固醇负反馈的变化，3）检查HPA轴的习惯与MR介导的临时临时临时相关的程度，以及HPA的压力习惯是否与HPA临时相关，并在HPA介导的范围内移动。与皮质类固醇受体表达的变化有关。 PI的直接职业目标是扩展其研究计划的质量，生产力和技术专业知识。 PI的长期职业目标是为理解影响压力反应的神经适应过程做出实质性的科学贡献。提出了一项职业发展计划，该计划将通过扩展PI在神经解剖学，细胞生物学，分子生物学和系统生理学领域中的合作和培训来帮助PI实现这些职业目标。在每个领域中，在每个领域中，都会提高知识，技术专长以及与专家的互动，对于PI实验室中的持续和未来研究至关重要，旨在果断地确定压力适应的基本机制。 PI的部门和机构致力于支持PI的研究计划，并提供了广泛的实验室空间和物理资源。通过部门批准的减少教学，K02奖将大大增加PI可以致力于他的研究和职业发展的时间和连贯的时间和连贯的时间，从而确保了这些努力的成功。