Herwig Annika, Revel Florent, Saboureau Michel, Pévet Paul, Steinlechner Stephan
Département de Neurobiologie des Rythme, Institut des Neurosciences Cellulaires et Intégratives, Université Louis Pasteur, IFR des Neurosciences de Strasbourg, France.
Chronobiol Int. 2006;23(1-2):269-76. doi: 10.1080/07420520500522424.
Circadian rhythms are still expressed in animals that display daily torpor, implying a temperature compensation of the pacemaker. Nevertheless, it remains unclear how the clock works in hypothermic states and whether torpor itself, as a temperature pulse, affects the circadian system. To reveal changes in the clockwork during torpor, we compared clock gene and neuropeptide expression by in situ hybridization in the suprachiasmatic nucleus (SCN) and pineal gland of normothermic and torpid Djungarian hamsters (Phodopus sungorus). Animals from light-dark (LD) 8ratio16 were sacrificed at 8 time points throughout 24 h. To investigate the effect of a previous torpor episode on the clock, we sacrificed a group of normothermic hamsters 1 day after torpor. In normothermic animals, Per1 peaked at zeitgeber time (ZT)4; whereas, Bmal1 reached maximal expression between ZT16 and ZT19. AVP mRNA in the SCN showed highest levels at ZT7. On the day of torpor, the levels of all mRNAs investigated, except for AVP mRNA, were increased during the torpor bout. Moreover, the Bmal1 rhythm was advanced. On the day after the hypothermia, Bmal1 and AVP rhythms showed severely depressed amplitude. Those distinct amplitude changes of Bmal1 and AVP on the day after a torpor episode expression suggests that torpor affects the circadian system, probably by altered translational processes that might lead to a modified protein feedback on gene expression. In the pineal gland, an important clock output, Aanat expression, peaked between ZT16 and ZT22 in normothermic animals. Aanat levels were significantly advanced on the day of hypothermia, an effect which was still visible 1 day afterward. In summary, this study showed that daily torpor affects the phase and amplitude of rhythmic clock gene and clock-controlled gene expression in the SCN. Furthermore, the rhythmic gene expression in a peripheral oscillator, the pineal gland, is also affected.
昼夜节律在表现出每日蛰伏的动物中仍然存在，这意味着生物钟起搏器具有温度补偿功能。然而，目前尚不清楚生物钟在低温状态下是如何工作的，以及蛰伏本身作为一个温度脉冲是否会影响昼夜节律系统。为了揭示蛰伏期间生物钟机制的变化，我们通过原位杂交比较了正常体温和蛰伏状态的黑线毛足鼠（Phodopus sungorus）视交叉上核（SCN）和松果体中生物钟基因和神经肽的表达。将处于16小时光照/8小时黑暗（LD 8:16）条件下的动物在24小时内的8个时间点处死。为了研究先前的蛰伏事件对生物钟的影响，我们在蛰伏1天后处死了一组正常体温的仓鼠。在正常体温的动物中，Per1在生物钟时间（ZT）4达到峰值；而Bmal1在ZT16和ZT19之间达到最大表达水平。SCN中的AVP mRNA在ZT7时水平最高。在蛰伏当天，除AVP mRNA外，所有检测的mRNA水平在蛰伏期间均升高。此外，Bmal1节律提前。在低温后的第二天，Bmal1和AVP节律的振幅严重降低。蛰伏事件后一天Bmal1和AVP表达的这些明显振幅变化表明，蛰伏可能通过改变翻译过程影响昼夜节律系统，这可能导致对基因表达的蛋白质反馈发生改变。在松果体中，作为重要的生物钟输出，Aanat表达在正常体温的动物中在ZT16和ZT22之间达到峰值。Aanat水平在低温当天显著提前，这种影响在一天后仍然可见。总之，这项研究表明，每日蛰伏会影响SCN中节律性生物钟基因和生物钟控制基因表达的相位和振幅。此外，外周振荡器松果体中的节律性基因表达也受到影响。
