IN VITRO REAL-TIME CIRCADIAN RHYTHM MEASUREMENT

体外实时昼夜节律测量

• 批准号: 7960778
• 负责人: CHIAKI FUKUHARA
• 金额: $ 1.3万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960778
• 关键词: Advanced Sleep Phase Syndrome; Biological Assay; Biopsy; Bipolar Disorder; Blood; Blood Cells; Blood specimen; Cells; Chemicals; Cicatrix; Circadian Rhythms; Clinical; Computer Retrieval of Information on Scientific Projects Database; Delayed Sleep Phase Syndrome; Dermal; Diagnostic; Disease; Fibroblasts; Funding; Future; Generations; Genetic; Grant; Health; Human; In Vitro; Institution; Left; Link; Malignant Neoplasms; Measurement; Measures; Mental disorders; Metabolic syndrome; Minority; Monitor; Pain; Participant; Pathogenesis; Patients; Pattern; Peripheral; Pharmacologic Substance; Physiological; Procedures; Recruitment Activity; Regulation; Reporter Genes; Reporting; Research; Research Personnel; Resources; Role; Seasonal Affective Disorder; Skin; Sleep Disorders; Source; System; Techniques; Testing; Time; United States National Institutes of Health; cell type; healthy volunteer; in vitro Assay; macrophage; 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. Circadian rhythm generation consists of an approximate 24 h rhythmic pattern of physiologic regulation whereby proper regulation of the expression is critical to maintaining good health. Disturbances in circadian rhythm generation appear to be associated with many diseases such as seasonal affective disorders, a variety of other mental illnesses, sleep problems, cancer, and a number of metabolic syndromes. It is possible that circadian disruptions have some causative role in the pathogenesis of several of these diseases, as there is evidence suggesting links between genetic factors related to abnormal circadian rhythm generation and illnesses like bipolar affective disorder, familial advanced sleep phase syndrome, and delayed sleep phase syndrome. Even though associations between circadian rhythm disturbances and several diseases have been reported in humans, the precise mechanisms by which circadian rhythm generation impacts the manifestation of disease remains unknown for many illnesses and disorders. Among the limiting factors are technical difficulties related to the physiological measurement of human circadian rhythm expression. To better understand human circadian rhythm generation in patients, the implications of circadian rhythm disturbances in pathogenesis, as well as to evaluate potential pharmaceutical treatments, it is important to develop a non-invasive, simple, rapid and reliable in vitro assay to determine circadian rhythm in humans. Recent findings have enabled investigators to demonstrate the feasibility of using peripheral cells to analyze human circadian rhythm. So far, the dermal fibroblast is the only peripheral cell in which stable circadian rhythm can be recorded in humans. However, skin biopsy is not a routine procedure in most clinical departments; they also are painful for patients and often leave scars. Therefore, it would be beneficial to develop an assay system using some other cell type (i.e., a blood cell). In the present proposal, we aim to develop a non-invasive, in vitro assay system to measure human circadian rhythm in macrophages derived from human blood samples, using real-time monitoring of circadian parameters with a clock gene reporter (a total of 31 healthy subjects will be recuited). Once the assay system is established, this technique will be applied to evaluate the effects of chemicals, thereby testing the feasibility of this assay as a future diagnostic tool (a total of 30 paritipants will be recuited). The CRC will be utilized to recruit healthy volunteers and collect blood samples for the above purpose. Each participant will be asked to donate 5 mL blood twice, at least one month apart.

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。 昼夜节律的产生由大约 24 小时的生理调节节律模式组成，因此适当的表达调节对于维持良好的健康至关重要。昼夜节律产生的紊乱似乎与许多疾病有关，例如季节性情感障碍、各种其他精神疾病、睡眠问题、癌症和许多代谢综合征。昼夜节律紊乱可能在其中几种疾病的发病机制中发挥一定的致病作用，因为有证据表明与昼夜节律异常产生相关的遗传因素与双相情感障碍、家族性睡眠时相提前综合征和睡眠延迟等疾病之间存在联系。相综合症。 尽管昼夜节律紊乱与人类多种疾病之间的关联已被报道，但对于许多疾病和紊乱，昼夜节律产生影响疾病表现的精确机制仍然未知。限制因素包括与人类昼夜节律表达的生理测量相关的技术困难。为了更好地了解患者人体昼夜节律的产生、昼夜节律紊乱在发病机制中的影响，以及评估潜在的药物治疗，开发一种非侵入性、简单、快速和可靠的体外测定法来确定昼夜节律非常重要在人类中。 最近的研究结果使研究人员能够证明使用外周细胞分析人类昼夜节律的可行性。迄今为止，真皮成纤维细胞是人类唯一可以记录稳定昼夜节律的外周细胞。然而，皮肤活检并不是大多数临床科室的常规程序；它们也会给患者带来痛苦，并且常常留下疤痕。因此，开发使用其他细胞类型（即血细胞）的测定系统将是有益的。 在本提案中，我们的目标是开发一种非侵入性体外测定系统，通过时钟基因报告器实时监测昼夜节律参数（总共 31 名健康人），测量源自人类血液样本的巨噬细胞的昼夜节律。科目将被重新征集）。一旦检测系统建立，该技术将用于评估化学物质的影响，从而测试该检测作为未来诊断工具的可行性（总共将招募30名参与者）。 CRC将用于招募健康志愿者并采集血液样本用于上述目的。每位参与者将被要求捐献两次 5 毫升血液，每次捐献至少间隔一个月。