Chronic effects of non-24 hour solar days - 公募研究
|研究課題名||Chronic effects of non-24 hour solar days|
An internal rhythm of close-to-24-hour (circadian) period has emerged in all life forms on Earth from the planet's rotational period. We now know that maintenance of the normal circadian rhythm is critical for physical as well as mental health. The circadian rhythm is a unique property of life on Earth as other planets in the solar system have vastly different solar day lengths. Mars, a major target of space colonization, for example, has a solar day length longer than 24 hours. However, long-term consequences of the non-24-hour day have not been examined. Chronic disturbance of circadian rhythms results in cognitive deficits, negative mood states and various metabolic problems. As an endophenotype of circadian rhythm disruption, we will examine the phase organization of circadian oscillations in brain tissues under unusual light-dark conditions and develop a model that predicts phase organizations under various non-Earth cycles.
We will first examine the distribution of phases in the brain circadian oscillators ("phase organization") under long and short days mimicking seasonal daylength conditions. This will be experimentally approached by monitoring bioluminescence rhythms in brain tissues expressing a circadian luciferase reporter, e.g., Bmal1-ELuc or PER2::LUC. The pathways that lead to a particular phase organization are thought to make an entangled network of feedback and feedforward motifs (Fig 1A), which synchronizes the circadian phases throughout the brain (Fig 1B). Understanding the nature of this network is critical for explaining potential disruptions in phase organization under unusual light-dark cycles (Fig 1C). We aim to construct a basic mathematical model that predicts a rough phase organization under a particular light-dark condition. This will form the basis of understanding the mechanism of altered phase organizations under chronic non-24 hours light-dark cycles.
Although the suprachiasmatic nucleus (SCN) has been known as the major circadian clock in the brain, studies have identified a number of extra-SCN circadian oscillators in the brain. In our previous study, we have shown that, as a consequence of a phase-repulsive coupling, a particular "phase map" is formed in the SCN under a particular daylength condition. We reason that the coupling motif can be universal and, much like the SCN, can create daylength-dependent changes in the phase organization among brain circadian oscillators. Together with our theoretical collaborators, we will determine if there exists a clustered pattern of phases among brain circadian oscillators and see if similarly clustered oscillators have similar intrinsic periods. We expect that these efforts will help us formulate a theoretical mechanism of the phase organization.
Fig 1. (A) Light information entered through the retina becomes an external cue for phase organization of circadian rhythms in the brain, which reaches a steady state through interactions with other parts of the body. (B) Under the 24-hour light-dark cycles, circadian rhythms in brain tissues maintain a roughly synchronized phase organization. (C) We examine if there is any disruption in the phase organization under unconventional light-dark cycles, including non-24-hour cycles.