Multiscale Time-resolved Analysis Reveals Remaining Behavioral Rhythms in Mice Without Canonical Circadian Clocks.
Multiscale Time-resolved Analysis Reveals Remaining Behavioral Rhythms in Mice Without Canonical Circadian Clocks.
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DOI：
10.1177/07487304221087065
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发表时间：
2022-06
影响因子：
3.5
通讯作者：
Stefanovska, Aneta
中科院分区：
文献类型：
--
作者：
Morris, Megan;Yamazaki, Shin;Stefanovska, Aneta
关键词：
昼夜节律是生物体内大约每24小时重复一次的内部过程。主导昼夜节律起搏器与环境光暗周期同步。其他昼夜节律起搏器，可以有非规范的昼夜节律机制，揭示了唤醒刺激，如定时喂养，可口的饭菜和运行轮访问，或甲基苯丙胺管理。生物体也有超昼夜节律，其周期短于昼夜节律。然而，超日节律的生物学机制、起源和功能意义尚未得到很好的阐明。占主导地位的昼夜节律往往掩盖了超昼夜节律，因此，我们通过敲除Per 1/2/3基因，其中Per 1和Per 2是哺乳动物光敏昼夜节律机制的重要组成部分，使小鼠的典型昼夜节律钟失效。此外，我们在272天的持续黑暗中记录了每分钟的车轮运行活动。然后，我们研究了在没有外部影响的情况下的节奏成分，采用独特的多尺度时间分辨方法来分析随时间变化的频率的振荡动力学。我们发现了四个节律成分，其周期分别为17 h、18 h、14 h和120 min。当17 h节律显著时，18 h节律的振幅较低。这种现象大约每2-3周周期性发生。我们发现，104小时和1020分钟的节奏是108小时节奏的谐波。脊提取的瞬时频率的耦合分析显示，从较慢的振荡（1017，1018，和1014小时）到较快的振荡（1020分钟）的强和稳定的相位耦合，弱和不太稳定的相位耦合在相反的方向和较慢的振荡之间。总之，这项研究阐明了振荡器之间的关系，在没有典型的昼夜节律钟，这是理解它们的功能意义的关键。这些研究是必不可少的，因为昼夜节律的破坏有助于疾病，如癌症和肥胖症，以及情绪障碍。
Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders.
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影响因子：
4.6
作者：
Flôres DE;Bettilyon CN;Yamazaki S
通讯作者：
Yamazaki S
影响因子：
4
作者：
Castellana S;Mazza T;Capocefalo D;Genov N;Biagini T;Fusilli C;Scholkmann F;Relógio A;Hogenesch JB;Mazzoccoli G
通讯作者：
Mazzoccoli G
影响因子：
2.5
作者：
DELPRAT, N;ESCUDIE, B;TORRESANI, B
通讯作者：
TORRESANI, B
影响因子：
20.6
作者：
Clemson, Philip;Lancaster, Gemma;Stefanovska, Aneta
通讯作者：
Stefanovska, Aneta
影响因子：
2.8
作者：
Dowse, Harold;Umemori, Juzoh;Koide, Tsuyoshi
通讯作者：
Koide, Tsuyoshi