Institut de Neurosciences Cellulaires et Intégratives, Département de Neurobiologie des Rythmes, Centre National de la Recherche Scientifique, UPR3212 associée à l'Université de Strasbourg, France.
Genes Brain Behav. 2010 Jul;9(5):467-77. doi: 10.1111/j.1601-183X.2010.00576.x. Epub 2010 Feb 17.
Animals fed daily at the same time exhibit circadian food-anticipatory activity (FAA), which has been suggested to be driven by one or several food-entrainable oscillators (FEOs). FAA is altered in mice lacking some circadian genes essential for timekeeping in the main suprachiasmatic clock (SCN). Here, we confirmed that single mutations of clock genes Per1(-/-) and Per2(Brdm1) alter FAA expression in constant darkness (DD) or under a light-dark cycle (LD). Furthermore, we found that Per1(-/-);Per2(Brdm1) and Per2(Brdm1);Cry1(-/-) double mutant animals did not display a stable and significant FAA either in DD or LD. Interestingly, rescued behavioural rhythms in Per2(Brdm1);Cry2(-/-) mice in DD were totally entrained to feeding time and re-synchronized after phase-shifts of mealtime, indicating a higher SCN sensitivity to feeding cues. However, under an LD cycle and restricted feeding at midday, FAA in double Per2(Brdm1);Cry2(-/-) mutant mice was absent. These results indicate that shutting down one or two clock genes results in altered circadian meal anticipation. Moreover, we show that in a genetically rescued SCN clock (Per2(Brdm1);Cry2(-/-)), food is a powerful zeitgeber to entrain behavioural rhythms, leading the SCN to be more sensitive to feeding cues than in wild-type littermates.
动物在每天同一时间进食会表现出昼夜节律性的食物预期活动(FAA),这种活动被认为是由一个或多个食物可诱导振荡器(FEOs)驱动的。在主要的视交叉上核(SCN)中,缺乏一些对计时至关重要的昼夜节律基因的小鼠中,FAA 会发生改变。在这里,我们证实了时钟基因 Per1(-/-) 和 Per2(Brdm1) 的单一突变会改变在持续黑暗(DD)或光-暗循环(LD)下 FAA 的表达。此外,我们发现 Per1(-/-);Per2(Brdm1) 和 Per2(Brdm1);Cry1(-/-) 双突变体动物在 DD 或 LD 中都没有表现出稳定而显著的 FAA。有趣的是,在 DD 中,Per2(Brdm1);Cry2(-/-) 小鼠中恢复的行为节律完全被喂食时间所同步,并在喂食时间的相位移动后重新同步,这表明 SCN 对喂食线索的敏感性更高。然而,在 LD 周期和限制在中午喂食时,双 Per2(Brdm1);Cry2(-/-) 突变小鼠的 FAA 则不存在。这些结果表明,关闭一个或两个时钟基因会导致昼夜节律性的进餐预期改变。此外,我们表明在基因修复的 SCN 时钟(Per2(Brdm1);Cry2(-/-))中,食物是一个强大的时间信号,可以使行为节律同步,使 SCN 对喂食线索的敏感性高于野生型同窝仔鼠。