The Research Institute for Time Studies, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8511, Japan.
Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Sci Rep. 2019 Jul 29;9(1):10909. doi: 10.1038/s41598-019-47053-3.
Lithium has been used as a mood stabilizer to treat human bipolar disorders for over half a century. Several studies have suggested the possibility that the efficacy of lithium treatment results in part from the amelioration of circadian dysfunction. However, the effect of lithium on clock gene expression has not yet been investigated in vivo because continuous measurement of gene expression in organs with high time resolution over a period of several days is difficult. To resolve this issue, we attached a small photo multiplier tube (PMT) tightly to the body surface of transgenic mice carrying a reporter gene such that the photon input window faced target organs such as the liver and kidney and succeeded in long-term continuous measurement of circadian gene expression in semi-freely moving mice over periods of several weeks. Using this simple method, we clearly showed that lithium causes circadian period elongation in peripheral clock gene expression rhythms in vivo. Further development of our detection system to maturity will aid a wide range of research fields in medicine and biology.
锂已被用作情绪稳定剂来治疗人类双相情感障碍半个多世纪了。一些研究表明，锂治疗的疗效部分可能源于对昼夜节律功能障碍的改善。然而，锂对生物钟基因表达的影响尚未在体内进行研究，因为连续测量多个天时间分辨率高的器官中的基因表达是很困难的。为了解决这个问题，我们将一个小型光电倍增管（PMT）紧紧地附着在携带报告基因的转基因小鼠的体表，使得光子输入窗口朝向肝脏和肾脏等靶器官，并成功地在数周的时间内对半自由活动的小鼠进行了昼夜节律基因表达的长期连续测量。使用这种简单的方法，我们清楚地表明，锂在体内导致外周时钟基因表达节律的昼夜周期延长。我们的检测系统进一步发展成熟将有助于医学和生物学的广泛研究领域。
