C H IN A Synchronization of peripheral circadian clocks in rats by external time cues

Circadian clocks are present in a variety of tissues and cells in mammals and appear to be organized in a hierarchical manner. They are divided into a master clock that is localized in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral clocks in extra-SCN brain regions and peripheral tissues, such as heart and liver. The circadian clock is generally reset by environmental time cues, such as light, food and temperature, in order to synchronize with the external time. The SCN clock is mainly entrained by the external light/dark (LD) cycle via the retinohypothalamic tract, which controls the circadian rhythms of mammalian behavior and physiology. Whereas the peripheral clocks seem to be reset mainly by food cues rather than the light cue, which controls the local circadian rhythm. However, the mechanisms by which light and food cues affect the re-entrainment of peripheral clocks have not yet been well known. Thus, to investigate whether and how the resetting processes of peripheral clocks are regulated by the light and food cues, we investigated both the individual and combined effects of these two external time cues on the synchronization of circadian gene expression in the peripheral clocks (pineal gland, liver, heart, kidney), and also on the phaseshift responses of locomotor activiy in rats. Chapter 1 Light and Food Cues Cooperate to Entrain the Rat Pineal Circadian Clock. Light and food signals are two dominant Zeitgeber for central and peripheral circadian clocks, respectively. However, whether and how changes in light and food stimuli affect circadian rhythms of mammalian pineal clock genes are still largely unknown. For the first time, in the present study, we established a method for analysis of the expression levels of most clock genes (Bmal1, Per1, Per2, Per3, Cry1, Dec1 and Dec2) and AANAT in a single rat pineal gland and used it to investigate individual and cooperative effects of feeding and light cycle