Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
Sci Rep. 2013;3:2074. doi: 10.1038/srep02074.
Evaluation of circadian phenotypes is crucial for understanding the pathophysiology of diseases associated with disturbed biological rhythms such as circadian rhythm sleep disorders (CRSDs). We measured clock gene expression in fibroblasts from individual subjects and observed circadian rhythms in the cells (in vitro rhythms). Period length of the in vitro rhythm (in vitro period) was compared with the intrinsic circadian period, τ, measured under a forced desynchrony protocol (in vivo period) and circadian/sleep parameters evaluated by questionnaires, sleep log, and actigraphy. Although no significant correlation was observed between the in vitro and in vivo periods, the in vitro period was correlated with chronotype, habitual sleep time, and preferred sleep time. Our data demonstrate that the in vitro period is significantly correlated with circadian/sleep preference. The findings suggest that fibroblasts from individual patients can be utilized for in vitro screening of therapeutic agents to provide personalized therapeutic regimens for CRSD patients.
评估生物钟表型对于理解与生物节律紊乱相关疾病的病理生理学（如昼夜节律睡眠障碍）至关重要。我们测量了个体受试者成纤维细胞中的时钟基因表达，并观察到细胞中的昼夜节律（体外节律）。体外节律的周期长度（体外周期）与强制去同步协议下测量的固有昼夜周期τ（体内周期）进行了比较，并通过问卷、睡眠日志和活动记录仪评估了昼夜节律/睡眠参数。尽管体外周期和体内周期之间没有观察到显著相关性，但体外周期与生物钟类型、习惯性睡眠时间和偏好睡眠时间相关。我们的数据表明，体外周期与昼夜节律/睡眠偏好显著相关。这些发现表明，个体患者的成纤维细胞可用于体外筛选治疗剂，为 CRSD 患者提供个体化的治疗方案。
