STRESS ALLOSTASIS: CRF, SEROTONIN AND THE BNST

应激失衡：CRF、血清素和 BNST

• 批准号: 8172346
• 负责人: DONALD G RAINNIE
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172346
• 关键词: Anxiety; Anxiety Disorders; Behavior; Chronic; Computer Retrieval of Information on Scientific Projects Database; Funding; Genetic; Grant; Green Fluorescent Proteins; Institution; Messenger RNA; Military Personnel; Modeling; Neurons; Physiological; Post-Traumatic Stress Disorders; Property; Research; Research Personnel; Resources; Role; Serotonin; Shock; Source; Stress; Transcript; Transgenic Mice; United States National Institutes of Health; Work; allostasis; combat; experience; in vivo; novel; response; restraint stress; serotonin receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In 2009 we continued to examine the role of the BNST in stress related anxiety disorders, and it's modulation by serotonin (5-HT). We have shown that repeated restraint stress (RRS) induces a significant disruption of 5-HT receptor mRNA transcripts in the BNST. Significantly, the disruption of 5-HT receptor mRNA correlates with the expression of enhanced anxiety-like behavior in vivo. We have extended this work to show that a similar response is observed following repeated unpredictable shock stress (USS) and, hence, the genetic disruption appears to generalize to chronic traumatic stress. Importantly, the USS paradigm closely resembles the daily experience of many military personnel in combat zones, and we believe that USS may accurately model the conditions that can induce PTSD in a subpopulation of combatants. Our prediction is that repeated traumatic stress results in a sensitization of CRF containing neurons in the BNST, which ultimately results in a pathological state of hyperarousal. We have developed a transgenic mouse that expresses a green fluorescent protein only in CRF neurons, and we are using this novel model to examine the effects of RSS and USS on the physiological properties of CRF containing neurons in the BNST.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在2009年，我们继续研究BNST在压力相关焦虑症中的作用，以及5-羟色胺（5-HT）的调节。 我们已经表明，重复束缚应激（RRS）诱导BNST的5-HT受体mRNA转录显着中断。 值得注意的是，5-HT受体mRNA的破坏与体内增强的焦虑样行为的表达相关。 我们已经扩展了这项工作，以表明在重复的不可预测的休克应激（USS）后观察到类似的反应，因此，遗传破坏似乎可以推广到慢性创伤应激。 重要的是，USS范式与许多军事人员在战区的日常经历非常相似，我们相信USS可以准确地模拟战斗人员亚群中诱发PTSD的条件。 我们的预测是，反复的创伤应激导致BNST中含有CRF的神经元的敏化，最终导致过度觉醒的病理状态。 我们已经开发了一种转基因小鼠，表达的绿色荧光蛋白，只在CRF神经元，我们正在使用这种新的模型来检查RSS和USS的影响，CRF的生理特性，在BNST的神经元。