Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation
Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation
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DOI：
10.1152/ajpregu.00697.2002
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发表时间：
2003-05-01
影响因子：
2.8
通讯作者：
Moyer, RW
中科院分区：
文献类型：
--
作者：
Kennaway, DJ;Voultsios, A;Moyer, RW
褪黑激素和车轮运行的节奏和急性和慢性光脉冲对这些节奏的影响进行了研究时钟（Delta 19）突变小鼠选择性繁殖合成褪黑激素。纯合褪黑激素熟练的Clock（Delta 19）突变小鼠（Clock（Delta 19/Delta 19）-MEL）有节奏地产生褪黑激素，峰值产生比野生型对照晚2小时（即，在灯亮之前）。相比之下，无论基因型如何，轮运行活动的发作时间发生在熄灯后20分钟内。突变体中褪黑激素的产生在预期的开灯时间的1小时内自发地下降。将小鼠置于连续黑暗中，褪黑激素节律持续存在，并且在前两个周期的每个周期中2小时后出现峰值，与突变体的内源性周期一致。这与车轮运行活动的开始形成对比，在持续的黑暗中几天都没有改变。在预期的光照时间前后的光脉冲，然后持续黑暗，将突变小鼠褪黑激素峰值的预期2小时延迟减少到接近1小时，并将野生型小鼠褪黑激素峰值的时间提前。当Clock（Delta 19/Delta 19）-MEL小鼠维持在每日15分钟光脉冲的骨架光周期中时，与褪黑激素缺陷突变体（9%）相比，更高比例（57%）被带入时间表。这些结果提供了令人信服的证据，即具有Clock（Delta 19）突变的小鼠表达基本上正常的节律性，尽管具有26-27小时的潜在内源性周期，并且它们可以通过短暂暴露于光而被夹带。他们还提出了关于时钟在节律性中的作用以及与激素节律相比监测行为节律的有用性的重要问题。
Melatonin and wheel-running rhythmicity and the effects of acute and chronic light pulses on these rhythms were studied in Clock(Delta19) mutant mice selectively bred to synthesize melatonin. Homozygous melatonin-proficient Clock(Delta19) mutant mice (Clock(Delta19/Delta19)-MEL) produced melatonin rhythmically, with peak production 2 h later than the wild-type controls (i.e., just before lights on). By contrast, the time of onset of wheel-running activity occurred within a 20-min period around lights off, irrespective of the genotype. Melatonin production in the mutants spontaneously decreased within 1 h of the expected time of lights on. On placement of the mice in continuous darkness, the melatonin rhythm persisted, and the peak occurred 2 h later in each cycle over the first two cycles, consistent with the endogenous period of the mutant. This contrasted with the onset of wheel-running activity, which did not shift for several days in constant darkness. A light pulse around the time of expected lights on followed by constant darkness reduced the expected 2-h delay of the melatonin peak of the mutants to similar to1 h and advanced the time of the melatonin peak in the wild-type mice. When the Clock(Delta19/Delta19)-MEL mice were maintained in a skeleton photoperiod of daily 15-min light pulses, a higher proportion entrained to the schedule (57%) than melatonin-deficient mutants (9%). These results provide compelling evidence that mice with the Clock(Delta19) mutation express essentially normal rhythmicity, albeit with an underlying endogenous period of 26-27 h, and they can be entrained by brief exposure to light. They also raise important questions about the role of Clock in rhythmicity and the usefulness of monitoring behavioral rhythms compared with hormonal rhythms.