Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México DF, México.
J Biol Rhythms. 2010 Dec;25(6):421-31. doi: 10.1177/0748730410383403.
Internal synchrony among external cycles and internal oscillators allows adaptation of physiology to cyclic demands for homeostasis. Night work and shift work lead to a disrupted phase relationship between external time cues and internal rhythms, also losing internal coherence among oscillations. This process results in internal desynchrony (ID) in which behavioral, hormonal, and metabolic variables cycle out of phase. It is still not clear whether ID originates at a peripheral or at a central level. In order to determine the possible role of hypothalamic oscillators in ID, we explored with a rat model of "night work" daily rhythms of activity and clock gene expression in the hypothalamus. This study provides evidence that wakefulness and activity during the normal resting phase lead to a shift in the diurnal rhythms of c-Fos and induce a rhythm of PER1 in the arcuate and dorsomedial nucleus of the hypothalamus, both associated with metabolism and regulation of the sleep/wake cycle. Moreover, the number of orexin (ORX)-positive neurons and c-Fos in the perifornical area increased during the working period, suggesting a relevant switch of activity in this brain region induced by the scheduled activity; however, the colocalization of c-Fos in ORX-positive cells was not increased. In contrast, the suprachiasmatic nucleus and the paraventricular nucleus remained locked to the light/dark cycle, resulting in ID in the hypothalamus. Present data suggest that ID occurs already at the level of the first output projections from the SCN, relaying nuclei that transmit temporal signals to other brain areas and to the periphery.
内外周期和内部振荡器之间的同步允许生理适应内稳态的周期性需求。夜班和轮班工作导致外部时间线索和内部节律之间的相位关系中断，内部振荡器之间也失去了连贯性。这个过程导致内部不同步（ID），其中行为、激素和代谢变量失去同步。目前尚不清楚 ID 是起源于外周还是中枢水平。为了确定下丘脑振荡器在 ID 中的可能作用，我们使用“夜班”大鼠模型探索了下丘脑的活动和时钟基因表达的日常节律。这项研究提供的证据表明，在正常休息期间的清醒和活动会导致 c-Fos 的昼夜节律发生转移，并诱导下丘脑弓状核和背内侧核中 PER1 的节律，这两者都与代谢和睡眠/觉醒周期的调节有关。此外，在工作期间，穹窿周区的食欲素（ORX）阳性神经元和 c-Fos 的数量增加，表明该脑区的活动发生了相关的转换，这种转换是由计划的活动引起的；然而，c-Fos 在 ORX 阳性细胞中的共定位没有增加。相比之下，视交叉上核和室旁核仍然与光/暗周期锁定，导致下丘脑的 ID。目前的数据表明，ID 已经发生在从 SCN 传出的第一级投射的水平上，中继核将时间信号传递到其他大脑区域和外周。
