Temporal profile of circadian clock gene expression in a transplanted suprachiasmatic nucleus and peripheral tissues.
ABSTRACT 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.
SourceAvailable from: Paul Pevet
Dataset: Plos.one 2009-4
[Show abstract] [Hide abstract]
ABSTRACT: Cimicifuga racemosa (L.) Nutt. (CR), known as black cohosh, has been used in Europe as a medicinal plant for more than a century and its roots have been widely used for the treatment of menopausal symptoms. Remifemin, the main ingredient in liquid or tablet medications prepared from isopropyl alcohol extracts of black cohosh rhizome, has also been evaluated in clinical studies. To observe changes in the expression of the c-Fos protein in the hypothalamic nuclei of four groups of rats-sham-operated group (SHAM), ovariectomized (OVX) group, ovariectomized group treated with estrogen(OVX+E), and ovariectomized group treated with the isopropanol extract of Cimicifuga racemosa (OVX+ICR)-and to investigate the mechanisms of black cohosh and estrogen that take place in the hypothalamic nuclei of ovariectomized rats. Fifty rats were assigned to each of the four groups and placed in incubators at 4 °C, 10 °C, 25 °C, 33 °C, or 38 °C for 2 h. They were then anesthetized, and their brains were removed after heart perfusion. c-Fos expression in the hypothalamic nuclei was evaluated using immunohistochemical methods. In the median preoptic nucleus (MnPO), ventromedial preoptic nucleus (VMPO), and suprachiasmatic nucleus (SCh) of the SHAM group, in the anterior hypothalamic area (AH) and supraoptic nucleus (SO) of all four groups, and in the paraventricular nucleus (PVN) of the SHAM, OVX and OVX+E groups, the c-Fos-positive cell densities all changed in a similar manner: the cell density decreased when the temperature was less than 25 °C and the density increased when the temperature was greater than 25 °C, demonstrating a V-type curve. The c-Fos density was lowest at 25°C. The other nuclei demonstrated irregular changes. The positive cell densities in the MnPO, AH, and PVN of the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX group at all temperatures, except 25 °C. Positive cell densities in the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX groups in the MPA at 25 °C, in the VMPO at 4 °C, 33 °C, and 38 °C, in the SO at 4 °C, 10 °C, and 38 °C, and in the SCh at 33 °C. Regardless of the temperature, positive cell densities were lower in the MnPO, MPA, VMPO, AH, SCh, SO, and PVN of the OVX groups in comparison with the densities measured in the same sites in the SHAM group. Following the administration of black cohosh and estrogen, the positive cell densities in the OVX groups increased and became closer to, or exceeded, those measured in the SHAM group, suggesting that both drugs may act on the hypothalamic nuclei and have therapeutic effects on menopausal symptoms.Journal of ethnopharmacology 06/2012; 142(3):769-75. DOI:10.1016/j.jep.2012.05.059 · 2.94 Impact Factor