Temporal profile of circadian clock gene expression in a transplanted suprachiasmatic nucleus and peripheral tissues

Department of Anatomy and Neurobiology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osakasayama City, Osaka 589-8511, Japan.
European Journal of Neuroscience (Impact Factor: 3.18). 12/2007; 26(10):2731-8. DOI: 10.1111/j.1460-9568.2007.05926.x
Source: PubMed


The mammalian hypothalamic suprachiasmatic nucleus (SCN) is the master oscillator that regulates the circadian rhythms of the peripheral oscillators. Previous studies have demonstrated that the transplantation of embryonic SCN tissues into SCN-lesioned arrhythmic mice restores the behavioral circadian rhythms of these animals. In our present study, we examined the clock gene expression profiles in a transplanted SCN and peripheral tissues, and also analysed the circadian rhythm of the locomotor activity in SCN-grafted mice. These experiments were undertaken to elucidate whether the transplanted SCN generates a dynamic circadian oscillation and maintains the phase relationships that can be detected in intact mice. The grafted SCN indeed showed dynamic circadian expression rhythms of clock genes such as mPeriod1 (mPer1) and mPeriod2 (mPer2). Furthermore, the phase differences between the expression rhythms of these genes in the grafted SCN and the locomotor activity rhythms of the transplanted animals were found to be very similar to those in intact animals. Moreover, in the liver, kidney and skeletal muscles of the transplanted animals, the phase angles between the circadian rhythm of the grafted SCN and that of the peripheral tissues were maintained as in intact animals. However, in the SCN-grafted animals, the amplitudes of the mPer1 and mPer2 rhythms were attenuated in the peripheral tissues. Our current findings therefore indicate that a transplanted SCN has the capacity to generate a dynamic intrinsic circadian oscillation, and can also lock the normal phase angles among the SCN, locomotor activity and peripheral oscillators in a similar manner as in intact control animals.

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    • "). In line with this idea, a recent study demonstrated that peripheral clock gene oscillations and their phase relation between organs were restored by SCN grafts despite “aberrant” locomotor activity (i.e., compared to intact animal) and disturbed endocrine rhythm [66], [67]. Interestingly, only a limited number of studies provided a real insight into the clock gene function, e.g., cell division [68], [69], chromatin remodeling [70] and haem metabolism [71]. "
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    ABSTRACT: The biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), controls the daily rhythms in physiology and behavior. Early studies demonstrated that light exposure not only affects the phase of the SCN but also the functional activity of peripheral organs. More recently it was shown that the same light stimulus induces immediate changes in clock gene expression in the pineal and adrenal, suggesting a role of peripheral clocks in the organ-specific output. In the present study, we further investigated the immediate effect of nocturnal light exposure on clock genes and metabolism-related genes in different organs of the rat. In addition, we investigated the role of the autonomic nervous system as a possible output pathway of the SCN to modify the activity of the liver after light exposure. First, we demonstrated that light, applied at different circadian times, affects clock gene expression in a different manner, depending on the time of day and the organ. However, the changes in clock gene expression did not correlate in a consistent manner with those of the output genes (i.e., genes involved in the functional output of an organ). Then, by selectively removing the autonomic innervation to the liver, we demonstrated that light affects liver gene expression not only via the hormonal pathway but also via the autonomic input. Nocturnal light immediately affects peripheral clock gene expression but without a clear correlation with organ-specific output genes, raising the question whether the peripheral clock plays a "decisive" role in the immediate (functional) response of an organ to nocturnal light exposure. Interestingly, the autonomic innervation of the liver is essential to transmit the light information from the SCN, indicating that the autonomic nervous system is an important gateway for the SCN to cause an immediate resetting of peripheral physiology after phase-shift inducing light exposures.
    Full-text · Article · Feb 2009 · PLoS ONE
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    ABSTRACT: The mammalian circadian pacemaker has been localized to the hypothalamic suprachiasmatic nucleus (SCN), where a set of clock genes and their resulting proteins form interlocking transcriptional/translational feedback loops to sustain molecular and functional oscillations. Interestingly, peripheral tissues and stimulated fibroblasts have also displayed daily oscillations, which are thought to be synchronized by the SCN in vivo. However, intercellular communications between the SCN and other tissues or cells remain poorly understood. Therefore, a novel co-culture model was established in the present study to understand the interactions between central and peripheral oscillators in co-cultures of SCN slices and NIH/3T3 cells in a serum-free condition. Expression profiles of Per1 and Rev-Erb alpha were measured in NIH/3T3 cells using real-time PCR. Results demonstrated that diffusible signals released from SCN slices could regulate molecular rhythms in cultured fibroblasts. Moreover, Rev-Erb alpha oscillation was more robust and appeared earlier than Per1.
    No preview · Article · Nov 2008 · Biochemical and Biophysical Research Communications
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