Department of Psychology, Michigan State University, East Lansing, MI 48824, USA; Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Neuroscience. 2011 Jun 2;183:99-107. doi: 10.1016/j.neuroscience.2011.03.041. Epub 2011 Apr 8.
Circadian rhythms, generated in the suprachiasmatic nucleus (SCN), are synchronized to the ambient light/dark (LD) cycle. Long-term disruptions in circadian rhythms are associated with many health problems. However, the underlying mechanisms for such pathologies are not well understood. In the present study, we utilized a chronic jet lag paradigm consisting of weekly 6 h phase shifts in the LD cycle to investigate the circadian responses in behavior and in the functioning of the SCN following long-term circadian perturbation, and to explore the duration and direction dependent changes of the SCN using rats subjected to weekly phase advances or delays. Wheel-running activity was monitored over four weekly phase advances. The nocturnal activity pattern was re-established by the end of each shift, and the rate for recovering the nocturnality appeared to accelerate following multiple shifts. SCN function was assessed by the expressions of the protein product of clock gene PER1 and of two putative SCN output signals, arginine vasopressin (AVP) and prokineticin2 (Pk2). At the end of the 4th weekly advance, the amplitude of the PER1 rhythm in the SCN decreased, and this reduction was more prominent in the dorsomedial SCN than in the ventrolateral SCN. The levels of AVP and Pk2 expression were also attenuated in the SCN and in targets of its efferent projections. Comparing rats subjected to four or eight shifts of either delay or advance, the results revealed that the responses of the SCN depended on both duration and direction of the shifts, such that the level of PER1 expression further decreased at the end of the 8th compared to the 4th phase advance, but did not change significantly following phase delays. Taken together, the results suggest that rhythm perturbation could compromise the time-keeping function of the SCN, which could contribute to the associated health issues.
昼夜节律由视交叉上核（SCN）产生，并与环境光照/黑暗（LD）周期同步。昼夜节律的长期紊乱与许多健康问题有关。然而，这种病理的潜在机制尚不清楚。在本研究中，我们利用慢性时差颠倒范式，每周进行 6 小时的 LD 周期相位移动，以研究长期昼夜节律干扰后行为和 SCN 功能的昼夜节律反应，并探索使用每周进行相位提前或延迟的大鼠的 SCN 随时间和方向的变化。监测了四轮每周相位提前的轮跑活动。每个移位结束时，夜间活动模式重新建立，并且在多次移位后，恢复夜间活动的速度似乎会加快。通过时钟基因 PER1 蛋白产物和两个假定的 SCN 输出信号（精氨酸加压素（AVP）和促动力素 2（Pk2）的表达来评估 SCN 功能。在第 4 次每周提前结束时，SCN 中 PER1 节律的振幅降低，并且背内侧 SCN 中的这种降低比腹外侧 SCN 更为明显。SCN 及其传出投射靶标的 AVP 和 Pk2 表达水平也减弱。比较进行 4 次或 8 次延迟或提前移位的大鼠，结果表明 SCN 的反应取决于移位的持续时间和方向，因此在第 8 次相位提前结束时，PER1 表达水平进一步降低，但在相位延迟后没有明显变化。总的来说，结果表明节律干扰可能会损害 SCN 的计时功能，这可能是相关健康问题的原因之一。
