Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent
Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent
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DOI：
10.1152/ajpregu.00223.2006
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发表时间：
2006-10-01
影响因子：
2.8
通讯作者：
Varcoe, Tamara J.
中科院分区：
文献类型：
--
作者：
Kennaway, David J.;Owens, Julie A.;Varcoe, Tamara J.
激素分泌、体温和睡眠/觉醒的昼夜节律性是由视交叉上核（SCN）中的时钟基因产生的神经活动的内源性节律引起的。这些基因之一，时钟，已被认为是必不可少的产生细胞的节律性中央和外围;然而，褪黑激素熟练时钟（德尔塔19）+ MEL突变小鼠保留褪黑激素的节律性，这表明他们的中央节律性是完整的。在这里，我们表明，褪黑激素的生产在这些突变体是有节奏的，在恒定的黑暗中，可以夹带由简短的单一的日常光脉冲。在正常光暗条件下，Clock（Delta 19）+ MEL小鼠SCN中per 2和prokineticin 2（PK 2）mRNA的表达呈节律性。Bmal 1和npas 2的表达没有改变，而per 1的表达则是抑制性的。与SCN相反，在正常光-暗条件下，Clock（Delta 19）+ MEL突变小鼠中per 1和per 2表达以及肝脏和骨骼肌中的Bmal 1表达以及血浆皮质酮是低水平的。npas 2 mRNA在肝脏中也呈节律性表达，而在肌肉中则呈节律性表达。时钟（德尔塔19）突变并没有取消中央节奏和轻夹带，这表明一个功能时钟同源物，可能npas 2，存在于SCN。然而，在组织中没有功能性Clock表达的情况下，Clock（Delta 19）+ MEL突变小鼠的SCN不能通过节律性输出（包括褪黑激素分泌）维持肝脏和肌肉节律性。因此，肝脏和肌肉，而不是SCN，对时钟有绝对的需求，而目前还不知道与时钟无关的因素能够产生后者。
The circadian rhythmicity of hormone secretion, body temperature, and sleep/wakefulness results from an endogenous rhythm of neural activity generated by clock genes in the suprachiasmatic nucleus (SCN). One of these genes, Clock, has been considered essential for the generation of cellular rhythmicity centrally and in the periphery; however, melatonin-proficient Clock(Delta 19) + MEL mutant mice retain melatonin rhythmicity, suggesting that their central rhythmicity is intact. Here we show that melatonin production in these mutants was rhythmic in constant darkness and could be entrained by brief single daily light pulses. Under normal light-dark conditions, per2 and prokineticin2 (PK2) mRNA expression was rhythmic in the SCN of Clock(Delta 19) + MEL mice. Expression of Bmal1 and npas2 was not altered, whereas per1 expression was arrhythmic. In contrast to the SCN, per1 and per2 expression, as well as Bmal1 expression in liver and skeletal muscle, together with plasma corticosterone, was arrhythmic in Clock(Delta 19) + MEL mutant mice in normal light- dark conditions. npas2 mRNA was also arrhythmic in liver but rhythmic in muscle. The Clock(Delta 19) mutation does not abolish central rhythmicity and light entrainment, suggesting that a functional Clock homolog, possibly npas2, exists in the SCN. Nevertheless, the SCN of Clock(Delta 19) + MEL mutant mice cannot maintain liver and muscle rhythmicity through rhythmic outputs, including melatonin secretion, in the absence of functional Clock expression in the tissues. Therefore, liver and muscle, but not SCN, have an absolute requirement for CLOCK, with as yet unknown Clock-independent factors able to generate the latter.