The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.-猫眼课题宝

DOI：

10.1371/journal.pone.0013376

发表时间：

2010-10-15

期刊：

PloS one

影响因子：

3.7

通讯作者：

中科院分区：

综合性期刊3区

文献类型：

作者：

Pagani L;Semenova EA;Moriggi E;Revell VL;Hack LM;Lockley SW;Arendt J;Skene DJ;Meier F;Izakovic J;Wirz-Justice A;Cajochen C;Sergeeva OJ;Cheresiz SV;Danilenko KV;Eckert A;Brown SA

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958564/?report=classic

人类的昼夜行为是由大脑下丘脑视交叉上核的生物钟周期长度决定的。然而，这种生物钟的细胞内在机制存在于身体的大多数细胞中。我们以前已经表明，对于极端的时钟型（“云雀”和“猫头鹰”）的个人，在人类成纤维细胞中测量的时钟特性与极端的昼夜行为相关。在这项研究中，我们已经测量了从正常个体中提取的人原代成纤维细胞的昼夜节律周期，并首次将其与在相同受试者体内测量的生理周期直接进行比较。通过两组不同视力受试者和一组全盲受试者的褪黑激素分泌模式，分别使用不同的方法估计人体生理周期长度。成纤维细胞周期长度通过慢病毒递送的昼夜节律报告基因的循环表达来测量。在每组内，生理学和成纤维细胞基因表达的昼夜节律周期长度之间观察到正线性相关。有趣的是，虽然盲人的成纤维细胞生物钟特性平均与正常人相同，但他们的生理周期明显更长。我们的结论是，人类昼夜节律行为的周期主要是由正常个体的细胞时钟特性驱动的，并且可以通过测量外周细胞如成纤维细胞来近似。基于有视力和失明受试者之间的差异，我们还推测，周期可以通过长时间的不寻常条件（如失明的完全光剥夺）进行修改。

Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype (“larks” and “owls”), clock properties measured in human fibroblasts correlated with extreme diurnal behavior. In this study, we have measured circadian period in human primary fibroblasts taken from normal individuals and, for the first time, compared it directly with physiological period measured in vivo in the same subjects. Human physiological period length was estimated via the secretion pattern of the hormone melatonin in two different groups of sighted subjects and one group of totally blind subjects, each using different methods. Fibroblast period length was measured via cyclical expression of a lentivirally delivered circadian reporter. Within each group, a positive linear correlation was observed between circadian period length in physiology and in fibroblast gene expression. Interestingly, although blind individuals showed on average the same fibroblast clock properties as sighted ones, their physiological periods were significantly longer. We conclude that the period of human circadian behaviour is mostly driven by cellular clock properties in normal individuals and can be approximated by measurement in peripheral cells such as fibroblasts. Based upon differences among sighted and blind subjects, we also speculate that period can be modified by prolonged unusual conditions such as the total light deprivation of blindness.