Postnatal constant light compensates Cryptochrome1 and 2 double deficiency for disruption of circadian behavioral rhythms in mice under constant dark.
Postnatal constant light compensates Cryptochrome1 and 2 double deficiency for disruption of circadian behavioral rhythms in mice under constant dark.
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DOI：
10.1371/journal.pone.0080615
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Honma K
中科院分区：
文献类型：
--
作者：
Ono D;Honma S;Honma K
时钟基因隐花色素（Cry 1）和Cry 2对于恒定黑暗（DD）下小鼠昼夜节律的表达是必需的。然而，在培养的新生Cry 1和Cry 2双缺陷（Cry 1-/-/Cry 2-/-）小鼠的视交叉上核（SCN）中，检测到时钟基因Per 1表达或时钟蛋白PER 2的昼夜节律。成年Cry 1-/-/Cry 2-/-小鼠缺乏昼夜节律很可能是由于SCN中振荡神经元的发育紊乱细胞耦合所致。另一方面，暴露于恒定光（LL）下的新生大鼠在长时间LL下形成了一个稳定的昼夜节律系统，这是已知的昼夜行为节律片段。在本研究中，Cry 1-/-/Cry 2-/-小鼠从出生后第1天起在LL下饲养7周，随后暴露于DD 3周。断乳后连续监测自发运动，并在长时间DD下从小鼠获得的培养SCN中测量PER 2：：LUC。令人惊讶的是，卡方周期图分析揭示了LL饲养的Cry 1-/-/Cry 2-/-小鼠中自发运动的显著昼夜节律，但未能检测到在光暗循环（LD）下饲养的Cry 1-/-/Cry 2-/-小鼠中的节律。相比之下，在成年期延长LL并没有拯救在LD提出的Cry 1-/-/Cry 2-/-小鼠的昼夜行为节律。视觉观察揭示了LL饲养的Cry 1-/-/Cry 2-/-小鼠在DD下的行为节律中具有不同周期的两种不同的活动成分：一种短于24小时，另一种长于24小时。这两种成分反复融合和分离。这些模式类似于野生型小鼠在长时间LL下的分裂行为节律。此外，在DD下的一些LL饲养的Cry 1-/-/Cry 2-/-小鼠中检测到PER 2：：LUC的昼夜节律。这些结果表明，新生儿暴露于LL补偿的CRY双重缺陷的昼夜行为节律的破坏下DD在成年期。
Clock genes Cryptochrome (Cry1) and Cry2 are essential for expression of circadian rhythms in mice under constant darkness (DD). However, circadian rhythms in clock gene Per1 expression or clock protein PER2 are detected in the cultured suprachiasmatic nucleus (SCN) of neonatal Cry1 and Cry2 double deficient (Cry1 -/-/Cry2 -/-) mice. A lack of circadian rhythms in adult Cry1 -/-/Cry2 -/- mice is most likely due to developmentally disorganized cellular coupling of oscillating neurons in the SCN. On the other hand, neonatal rats exposed to constant light (LL) developed a tenable circadian system under prolonged LL which was known to fragment circadian behavioral rhythms. In the present study, Cry1 -/-/Cry2 -/- mice were raised under LL from postnatal day 1 for 7 weeks and subsequently exposed to DD for 3 weeks. Spontaneous movement was monitored continuously after weaning and PER2::LUC was measured in the cultured SCN obtained from mice under prolonged DD. Surprisingly, Chi square periodogram analysis revealed significant circadian rhythms of spontaneous movement in the LL-raised Cry1 -/-/Cry2 -/- mice, but failed to detect the rhythms in Cry1 -/-/Cry2 -/- mice raised under light-dark cycles (LD). By contrast, prolonged LL in adulthood did not rescue the circadian behavioral rhythms in the LD raised Cry1 -/-/Cry2 -/- mice. Visual inspection disclosed two distinct activity components with different periods in behavioral rhythms of the LL-raised Cry1-/-/Cry2-/- mice under DD: one was shorter and the other was longer than 24 hours. The two components repeatedly merged and separated. The patterns resembled the split behavioral rhythms of wild type mice under prolonged LL. In addition, circadian rhythms in PER2::LUC were detected in some of the LL-raised Cry1-/-/Cry2-/- mice under DD. These results indicate that neonatal exposure to LL compensates the CRY double deficiency for the disruption of circadian behavioral rhythms under DD in adulthood.
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