Microcurrent stimulation activates the circadian machinery in mice

Abstract

The circadian rhythm, which regulates various body functions, is transcriptionally controlled by a series of clock gene clusters. The clock genes are related to the pathology of various kinds of diseases, which in turn, is related to aging. Aging in humans is a worldwide problem; it induces sleep disorders and disruption of the circadian rhythm. It also decreases ocular vision and appetite and weakens the synchronization of clock genes by light and food. Therefore, a simple method for the synchronization of clock genes in the body is required. In this study, the influence of microcurrent stimulation (MCS) on the circadian machinery in wild-type (WT) and Clock mutant (Clk/Clk) mice was investigated. MCS induced Per1 mRNA expression in cultured mouse astrocytes; cAMP response element (CRE) in the Per1 mouse promoter was found to be important for the induction of Per1 mRNA. In addition, MCS increased the Per1 mRNA levels in mouse livers and caused the phase advance of the Per1 expression rhythm. The protein expression rhythm of phosphor-cAMP response element-binding protein (pCREB) was altered and the phase of expression of pCREB protein advanced. Finally, the influence of MCS on the locomotor activity rhythm in WT and Clk/Clk mice was investigated. MCS caused the phase advance of the locomotor activity rhythm in WT and Clk/Clk mice. The results of this study indicate that MCS activated the clock machinery in mice; MCS may thus improve the quality of new treatment modalities in the future.

Keywords: Circadian rhythm; Microcurrent stimulation; Period; cAMP response element-binding protein.