Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny.
Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny.
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DOI：
10.1111/j.1460-9568.2008.06605.x
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
von Gall C
中科院分区：
文献类型：
--
作者：
Ansari N;Agathagelidis M;Lee C;Korf HW;von Gall C
哺乳动物许多身体功能的昼夜节律是由位于下丘脑视交叉上核（SCN）的主起搏器控制的，该起搏器同步外周振荡。SCN和外周振荡子共享分子时钟的几个组成部分，包括转录激活因子（BMAL1和CLOCK/NPAS2）和抑制剂（mPER1/2和mCRY1/2）。在这里，我们比较了SCN和结节部（PT）中生物钟的个体发育成熟。PT是一种外围振荡器，强烈依赖于节律性褪黑激素信号。在小鼠个体发育的四个不同阶段（胎儿（胚胎第18天）、新生儿（2日龄）、婴儿（10日龄）和成年）的四个不同时间点，测定SCN和PT中时钟基因蛋白的免疫反应。在胎儿SCN中，除BMAL1外，所有时钟蛋白的免疫反应水平均显著低于成人水平。在新生儿SCN中，时钟蛋白免疫反应尚未达到成人水平，但婴儿SCN显示出与成人相似的免疫反应水平。相比之下，胎儿PT中所有时钟基因蛋白的免疫反应与新生儿、婴儿和成人一样强烈，并且表现出相同的阶段。由于胎儿松果体还不能有节奏地产生褪黑激素，胎儿PT中时钟基因蛋白的节律可能依赖于母体褪黑激素信号。因此，我们的数据提供了第一个证据，证明母体褪黑素对建立和维持胎儿外周振荡器的昼夜节律很重要。
Circadian rhythms of many body functions in mammals are controlled by a master pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN) that synchronises peripheral oscillators. The SCN and peripheral oscillators share several components of the molecular clockwork and comprise transcriptional activators (BMAL1 and CLOCK/NPAS2) and inhibitors (mPER1/2 and mCRY1/2). Here we compared the ontogenetic maturation of the clockwork in the SCN and pars tuberalis (PT). The PT is a peripheral oscillator that strongly depends on rhythmic melatonin signals. Immunoreactions for clock gene proteins were determined in the SCN and PT at four different timepoints during four differential stages of mouse ontogeny: foetal (embryonic day 18), newborn (2-day-old), infantile (10-day-old), and adult. In the foetal SCN levels of immunoreactions of all clock proteins were significantly lower as compared to adult levels except for BMAL1. In the newborn SCN the clock protein immunoreactions had not yet reached adult levels, but the infantile SCN showed similar levels of immunreactions as the adult. In contrast, immunoreactions for all clock gene proteins in the foetal PT were as intense as in newborn, infantile, and adult and showed the same phase. As the foetal pineal gland is not yet capable of rhythmic melatonin production, the rhythms in clock gene proteins in the foetal PT are presumably dependent on the maternal melatonin signal. Thus, our data provide the first evidence that maternal melatonin is important for establishing and maintaining circadian rhythms in a foetal peripheral oscillator.
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