In vivo evaluation of the effect of lithium on peripheral circadian clocks by real-time monitoring of clock gene expression in near-freely moving mice

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.