In vitro circadian period is associated with circadian/sleep preference

Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
Scientific Reports (Impact Factor: 5.58). 06/2013; 3:2074. DOI: 10.1038/srep02074
Source: PubMed


Evaluation of circadian phenotypes is crucial for understanding the pathophysiology of diseases associated with disturbed biological rhythms such as circadian rhythm sleep disorders (CRSDs). We measured clock gene expression in fibroblasts from individual subjects and observed circadian rhythms in the cells (in vitro rhythms). Period length of the in vitro rhythm (in vitro period) was compared with the intrinsic circadian period, τ, measured under a forced desynchrony protocol (in vivo period) and circadian/sleep parameters evaluated by questionnaires, sleep log, and actigraphy. Although no significant correlation was observed between the in vitro and in vivo periods, the in vitro period was correlated with chronotype, habitual sleep time, and preferred sleep time. Our data demonstrate that the in vitro period is significantly correlated with circadian/sleep preference. The findings suggest that fibroblasts from individual patients can be utilized for in vitro screening of therapeutic agents to provide personalized therapeutic regimens for CRSD patients.

Download full-text


Available from: Masaaki Ikeda
  • Source
    • "Compared to PLR, a more complicated mechanism and more factors are involved in sleep. For instance, inter-individual differences in endogenous circadian rhythm, circadian phase and sleep timing have been reported [30,31]. Furthermore, contribution of the CLOCK gene to circadian phenotypes, particularly sleep timing, has been reported [32,33]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background In our previous studies, we found that the Ile394Thr SNP in the melanopsin gene (OPN4) was functionally associated with the pupillary light reflex. This indicates the possibility that OPN4*Ile394Thr is associated with other non-image forming responses. The aim of this study was therefore to determine whether OPN4*Ile394Thr is associated with sleep/wake timing. Methods A total of 348 healthy Japanese university students participated in this study. Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits, including bedtime, wake time and sleep duration, were assessed separately for weekdays and weekends. A total of 328 samples, including 223 samples with TT genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical analysis. No significant difference in age or male/female distribution was found among the three genotype groups. Results There was no significant difference in circadian preference among the genotype groups. During weekdays, bedtime, wake time and midpoint of sleep for CC subjects were significantly later than those for TT and TC subjects. However, there was no difference between TT and TC subjects in any of their sleep habits. During weekends, bedtime of CC subjects was significantly later than those of TT and TC subjects, and the midpoint of sleep of CC subjects was significantly later than that of TC subjects. Conclusions Our findings demonstrated that OPN4*Ile394Thr is associated with sleep/wake timing. We also found that the sleep/wake timing of subjects with the CC genotype was later than that of subjects with the TT or TC genotype.
    Full-text · Article · May 2014 · Journal of PHYSIOLOGICAL ANTHROPOLOGY
  • Source

    Full-text · Article · Jan 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Impairment of clock gene expression and changes in melatonin and 17-β-estradiol levels may constitute biological alterations underlying the increased risk of breast cancer among shift workers. The aim of this study was to compare levels of selected core clock gene expression, 6-sulfatoxymelatonin (aMT6s), and 17-β-estradiol between rotational shift work (SW) and daytime (DT) workers after a day off. The cross-sectional study comprised 60 nurses with ≥2 years of SW and 56 permanent DT nurses. Transcript levels of circadian genes BMAL1, CLOCK, NPAS2, CRY1, CRY2, PER1, PER2, PER3, and REVERBα were determined by quantitative real-time polymerase chain reaction (PCR) in lymphocytes. All participants were tested in the early follicular phase of the menstrual cycle. Samples were collected at the beginning of the morning-shift after a regular night's sleep on a day off. Chronotype and sociodemographic characteristics were also evaluated. We found a significantly higher expression of BMAL1, CLOCK, NPAS2, PER1, PER2, and REVERBα and a lower expression of PER3, CRY1 and CRY2 among SW compared to DT nurses. SW participants did not demonstrate a significant difference in aMT6s levels, but they did show significantly higher 17-β-estradiol levels compared to DT nurses. Multiple linear regression analysis confirmed the role of SW on expression of BMAL1 (β 0.21, P=0.040), CLOCK (β 0.35, P=0.008), NPAS2 (β 0.30, P=0.012), PER1 (β 0.33, P=0.008), PER2 (β 0.19, P=0.047), PER3 (β -0.27, P=0.012), CRY1 (β -0.33, P=0.002), CRY2 (β -0.31, P=0.005), REVERBα (β 0.19, P=0.045), and on 17-β-estradiol levels (β 0.32, P=0.003). The analysis also confirmed the role of chronotype as an independent factor for PER1 (β 0.48, P=0.001) and PER2 (β -0.22, P=0.022) expression, and 17-β-estradiol levels (β 0.26, P=0.011). Rotating SW nurses show alterations in peripheral clock gene expression and 17-β-estradiol levels at the beginning of the morning shift after a day off.
    Full-text · Article · Jan 2014 · Scandinavian Journal of Work, Environment & Health
Show more