GENE SILENCING IN THE RHESUS MACAQUE USING LENTIVIRAL VECTORS

使用慢病毒载体对恒河猴进行基因沉默

• 批准号: 7716009
• 负责人: HENRYK F URBANSKI
• 金额: $ 2.77万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716009
• 关键词: Adrenal Glands; Biological Clocks; Brain; Circadian Rhythms; Computer Retrieval of Information on Scientific Projects Database; Depth; Disease; Disruption; Elderly; Etiology; Funding; Future; Gene Silencing; Generations; Goals; Grant; Human; Institution; Kidney; Laboratories; Lentivirus Vector; Liver; Macaca mulatta; Metabolism; Molecular; Neurosecretory Systems; Pacemakers; Peripheral; Phase; Physiologic Thermoregulation; Physiological; Physiology; Pilot Projects; Primates; Research; Research Personnel; Resources; Seasonal Affective Disorder; Sleep; Sleep Wake Cycle; Source; Stress; Thinking; United States National Institutes of Health; novel; response; stem; suprachiasmatic nucleus; therapy development; tool

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. Major physiological functions, such as metabolism, thermoregulation, sleep, and response to stress, all have a circadian rhythm. Moreover, disruption of these rhythms is thought to contribute to the etiology of perturbed sleep-wake cycles in the elderly and to Seasonal Affective Disorder (SAD). However, the underlying neuroendocrine mechanisms responsible for coordinating rhythmic functions in humans are poorly understood. Recently, my laboratory discovered that circadian rhythms in the rhesus monkey are controlled not only by a central pacemaker, located in the suprachiasmatic nucleus (SCN) of the brain, but also by peripheral oscillators in the adrenal gland, liver and kidneys. Taken together, these novel findings imply that normal physiological functions are regulated by coordinated actions of several distinct biological clocks, and that various disease states may stem from abnormal phase relationships between them. To develop effective therapies for circadian-related disorders in humans, we need to have a deeper understanding of the molecular mechanisms responsible for circadian rhythm generation in primates, and a deeper understanding of how peripheral oscillators synchronize their rhythmic activity. The goal of this pilot study is to develop an effective way of selectively silencing specific body clocks. This powerful tool would enable us to systematically examine the contribution of the various peripheral oscillators to normal physiology and to lay the groundwork for future development of therapies for circadian-related disorders.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 主要的生理功能，例如代谢，温度调节，睡眠和对压力的反应，都具有昼夜节律。此外，这些节奏的破坏被认为有助于老年人和季节性情感障碍的扰动睡眠效果周期的病因（SAD）。但是，对人类有节奏功能的负责协调节奏功能的潜在神经内分泌机制知之甚少。最近，我的实验室发现，恒河猴中的昼夜节律不仅由位于大脑上核核（SCN）的中央起搏器控制，而且还由肾上腺，肝脏和肾脏的外围振荡器控制。综上所述，这些新颖的发现表明，正常的生理功能受几种不同生物时钟的协调作用调节，并且各种疾病状态可能源于它们之间的异常相位关系。为了开发针对人类中昼夜节律相关疾病的有效疗法，我们需要更深入地了解造成灵长类动物中昼夜节律产生的分子机制，以及对外围振荡者如何同步其节奏活性的更深入了解。这项试验研究的目的是开发一种有效的方式，使特定的身体时钟有效。这种强大的工具将使我们能够系统地检查各种外围振荡器对正常生理学的贡献，并为未来开发与昼夜节律相关疾病的疗法开发奠定基础。