Robust food anticipatory activity in BMAL1-deficient mice.

Robust food anticipatory activity in BMAL1-deficient mice.
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DOI:
10.1371/journal.pone.0004860
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Yamazaki S
Yamazaki S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pendergast JS;Nakamura W;Friday RC;Hatanaka F;Takumi T;Yamazaki S

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食物供应是一个强有力的环境线索,指导啮齿动物的昼夜运动活动。尽管夜行性啮齿类动物更喜欢在夜间觅食,但白天的食物预期活动(FAA)在一天中预定时间提供的短餐之前被观察到。在这种限制进食的情况下,啮齿动物表现出两种不同的活动,一种是夜间活动节奏,受视交叉上核(SCN)的主时钟控制,受光-暗周期的影响,另一种是白天活动节奏,与用餐时间相锁定。FAA也发生在食物剥夺期间,这表明食物可携带振荡器(FEO)在没有预定喂养的情况下保持时间。先前的研究表明,FEO在解剖学上与SCN不同,并且在缺乏SCN中保持时间所需的一些昼夜节律基因的小鼠中观察到FAA。在目前的研究中,我们优化了在缺乏功能性BMAL1的小鼠中限制喂养和食物剥夺时检测FAA的条件,BMAL1在SCN中昼夜节律的产生至关重要。我们发现bmal1缺陷小鼠在12h光照:12h黑暗(12L:12D)和18L:6D光照周期的限制进食期间显示FAA,但在食物剥夺期间仅在18L:6D观察到明显的活性。虽然缺乏bmal1的小鼠在持续黑暗的受限喂养中也表现出强大的FAA,但小鼠在食物剥夺期间过度活跃,因此尚不清楚FAA是否始终发生在先前计划的食物供应时间。综上所述,我们的研究结果表明,优化实验条件(如光周期)可能是必要的,以可视化转基因小鼠的FAA。此外,FAA的表达可能没有依赖于BMAL1的昼夜节律振荡器。
Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Even though nocturnal rodents prefer to forage at night, daytime food anticipatory activity (FAA) is observed prior to short meals presented at a scheduled time of day. Under this restricted feeding regimen, rodents exhibit two distinct bouts of activity, a nocturnal activity rhythm that is entrained to the light-dark cycle and controlled by the master clock in the suprachiasmatic nuclei (SCN) and a daytime bout of activity that is phase-locked to mealtime. FAA also occurs during food deprivation, suggesting that a food-entrainable oscillator (FEO) keeps time in the absence of scheduled feeding. Previous studies have demonstrated that the FEO is anatomically distinct from the SCN and that FAA is observed in mice lacking some circadian genes essential for timekeeping in the SCN. In the current study, we optimized the conditions for examining FAA during restricted feeding and food deprivation in mice lacking functional BMAL1, which is critical for circadian rhythm generation in the SCN. We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D. While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability. Taken together, our findings suggest that optimization of experimental conditions such as photoperiod may be necessary to visualize FAA in genetically modified mice. Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1.
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