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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 2009 年，我们继续研究 BNST 在压力相关焦虑症中的作用及其受血清素 (5-HT) 的调节。 我们已经证明，重复的束缚应激 (RRS) 会导致 BNST 中 5-HT 受体 mRNA 转录物的显着破坏。 值得注意的是，5-HT 受体 mRNA 的破坏与体内焦虑样行为增强的表达相关。 我们扩展了这项工作，以表明在重复的不可预测的冲击应激（USS）后观察到类似的反应，因此，遗传破坏似乎普遍适用于慢性创伤应激。 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 可以准确地模拟可能在战斗人员亚群中诱发 PTSD 的条件。 我们的预测是，反复的创伤性应激会导致 BNST 中含有 CRF 的神经元变得敏感，最终导致过度唤醒的病理状态。 我们开发了一种仅在 CRF 神经元中表达绿色荧光蛋白的转基因小鼠，并且我们正在使用这种新模型来检查 RSS 和 USS 对 BNST 中含有 CRF 的神经元的生理特性的影响。