Timed hypocaloric feeding and melatonin synchronize the suprachiasmatic clockwork in rats, but with opposite timing of behavioral output

Timed hypocaloric feeding and melatonin synchronize the suprachiasmatic clockwork in rats, but with opposite timing of behavioral output
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DOI:
10.1111/j.1460-9568.2005.04284.x
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发表时间:
2005-08-01
影响因子:
3.4
通讯作者:
Challet, E
Challet, E
中科院分区:
医学3区
文献类型:
--
作者:
Caldelas, I;Feillet, CA;Challet, E

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时间组织的分子钟表和行为输出进行了研究,在夜间大鼠在恒定的黑暗和同步nonphotic线索(每日normocaloric或低热量的喂养和褪黑激素输注)或光(光暗周期和每日1小时光照)。在24 h内检测视交叉上核中时钟基因(Per 1、Per 2和Bmal 1)和时钟控制基因(加压素)的表达。光和外源褪黑激素同步的分子时钟,信号,分别为“白天”和“夜间”,而不影响时间组织的行为输出(休息/活动节奏)。相比之下,同步到低热量喂养导致视交叉上时钟的基因表达和运动活动节律的波形之间的显着的时间变化,大鼠然后在主观的一天变得活跃(日样时间组织)。当喂食时间与活动偏移相吻合时,正常热量喂食也同步了自发活动节律,时间组织没有明显的转换。梨状皮质中Per 2表达的峰值发生在活动/进食期的开始和中间之间,取决于同步器。这些数据表明,即使视交叉上的时钟装置可以同步到非光的线索,低热量喂养可能会从下游的时钟基因振荡在视交叉上核产生一个稳定的,但相反的组织的休息/活动周期。
Temporal organization of the molecular clockwork and behavioral output were investigated in nocturnal rats housed in constant darkness and synchronized to nonphotic cues (daily normocaloric or hypocaloric feeding and melatonin infusion) or light (light-dark cycle and daily 1-h light exposure). Clock gene (Per1, Per2 and Bmal1) and clock-controlled gene (Vasopressin) expression in the suprachiasmatic nuclei was assessed over 24 h. Light and exogenous melatonin synchronized the molecular clock, signaling, respectively, 'daytime' and 'nighttime', without affecting temporal organization of behavioral output (rest/activity rhythm). By contrast, synchronization to hypocaloric feeding led to a striking temporal change between gene expression in the suprachiasmatic clock and waveform of locomotor activity rhythm, rats then becoming active during the subjective day (diurnal-like temporal organization). When the time of feeding coincided with activity offset, normocaloric feeding also synchronized the locomotor activity rhythm with no apparent switch in temporal organization. Peak of Per2 expression in the piriform cortex occurred between the beginning and the middle of the activity/feeding period, depending on the synchronizer. These data demonstrate that even though the suprachiasmatic clockwork can be synchronized to nonphotic cues, hypocaloric feeding likely acts downstream from clock gene oscillations in the suprachiasmatic nuclei to yield a stable yet opposite organization of the rest/activity cycle.