Article

Molecular mechanism of suppression of circadian rhythms by a critical stimulus.

Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
The EMBO Journal (Impact Factor: 10.75). 12/2006; 25(22):5349-57. DOI: 10.1038/sj.emboj.7601397
Source: PubMed

ABSTRACT Circadian singularity behavior (also called suppression of circadian rhythms) is a phenomenon characterized by the abolishment of circadian rhythmicities by a critical stimulus. Here we demonstrate that both temperature step up and light pulse, stimuli that activate the expression of the Neurospora circadian clock gene frequency (frq), can trigger singularity behavior in this organism. The arrhythmicity is transient and is followed by the resumption of rhythm in randomly distributed phases. In addition, we show that induction of FRQ expression alone can trigger singularity behavior, indicating that FRQ is a state variable of the Neurospora circadian oscillator. Furthermore, mutations of frq lead to changes in the amplitude of FRQ oscillation, which determines the sensitivity of the clock to phase-resetting cues. Our results further suggest that the singularity behavior is due to the loss of rhythm in all cells. Together, these data suggest that the singularity behavior is due to a circadian negative feedback loop driven to a steady state after the critical treatment. After the initial arrhythmicity, cell populations are then desynchronized.

Download full-text

Full-text

Available from: Guocun Huang, Apr 17, 2015
1 Follower
 · 
88 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The bedtime of preschoolers/pupils/students in Japan has become progressively later with the result sleep duration has become progressively shorter. With these changes, more than half of the preschoolers/pupils/students in Japan recently have complained of daytime sleepiness, while approximately one quarter of junior and senior high school students in Japan reportedly suffer from insomnia. These preschoolers/pupils/students may be suffering from behaviorally induced insufficient sleep syndrome due to inadequate sleep hygiene. If this diagnosis is correct, they should be free from these complaints after obtaining sufficient sleep by avoiding inadequate sleep hygiene. However, such a therapeutic approach often fails. Although social factors are often involved in these sleep disturbances, a novel clinical notion – asynchronization – can further a deeper understanding of the pathophysiology of these disturbances. The essence of asynchronization is a disturbance in various aspects (e.g., cycle, amplitude, phase and interrelationship) of the biological rhythms that normally exhibit circadian oscillation, presumably involving decreased activity of the serotonergic system. The major trigger of asynchronization is hypothesized to be a combination of light exposure during the night and a lack of light exposure in the morning. In addition to basic principles of morning light and an avoidance of nocturnal light exposure, presumable potential therapeutic approaches for asynchronization involve both conventional ones (light therapy, medications (hypnotics, antidepressants, melatonin, vitamin B12), physical activation, chronotherapy) and alternative ones (kampo, pulse therapy, direct contact, control of the autonomic nervous system, respiration (qigong, tanden breathing), chewing, crawling). A morning-type behavioral preference is described in several of the traditional textbooks for good health. The author recommends a morning-type behavioral lifestyle as a way to reduce behavioral/emotional problems, and to lessen the likelihood of falling into asynchronization.
    Brain & development 04/2009; DOI:10.1016/j.braindev.2008.07.006 · 1.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circadian rhythms are endogenous oscillations characterized by a period of about 24h. They constitute the biological rhythms with the longest period known to be generated at the molecular level. The abundance of genetic information and the complexity of the molecular circuitry make circadian clocks a system of choice for theoretical studies. Many mathematical models have been proposed to understand the molecular regulatory mechanisms that underly these circadian oscillations and to account for their dynamic properties (temperature compensation, entrainment by light dark cycles, phase shifts by light pulses, rhythm splitting, robustness to molecular noise, intercellular synchronization). The roles and advantages of modeling are discussed and illustrated using a variety of selected examples. This survey will lead to the proposal of an integrated view of the circadian system in which various aspects (interlocked feedback loops, inter-cellular coupling, and stochasticity) should be considered together to understand the design and the dynamics of circadian clocks. Some limitations of these models are commented and challenges for the future identified.
    Central European Journal of Biology 10/2011; 6(5). DOI:10.2478/s11535-011-0062-4 · 0.63 Impact Factor
  • Source