Mice hypomorphic for Pitx3 show robust entrainment of circadian behavioral and metabolic rhythms to scheduled feeding.
Mice hypomorphic for Pitx3 show robust entrainment of circadian behavioral and metabolic rhythms to scheduled feeding.
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DOI：
10.1016/j.celrep.2021.109865
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发表时间：
2022-01-11
期刊：
影响因子：
8.8
通讯作者：
Steele AD
中科院分区：
文献类型：
--
作者：
Scarpa LL;Wanken B;Smidt M;Mistlberger RE;Steele AD
pitx 3ak小鼠缺乏功能性视网膜，黑质中的多巴胺神经元不到10%。报道，在这些小鼠中不存在昼夜节律对每日光-暗（LD）周期的夹带，并且运动活动、能量消耗和其他代谢变量的节律被随意获得的食物破坏，并且不能夹带每日喂养。作者提出视交叉上核的视网膜神经支配是循环代谢稳态发展所必需的，但方法学问题限制了对结果的解释。使用标准化的喂养时间表和程序区分自由运行的昼夜节律，我们证实，Pitx 3ak小鼠的行为和代谢节律不夹带到LD周期，但我们发现没有损害昼夜代谢的组织与食物自由采食，并没有损害夹带代谢或行为节律的日常喂养时间表。这篇论文是对发表在《细胞报告》上的论文的回应。另见本期发表的回应。Scarpa等人证明，尽管已经报道过，Pitxak突变小鼠确实会将行为和代谢带入预定的喂养。这些研究之间的关键方法差异进行了讨论，长期的，热量限制的喂养条件是必不可少的适当可视化的行为夹带预定喂养。值得注意的是，尽管黑质中的多巴胺神经元非常少，几乎完全缺乏晶状体和视网膜功能，Pitx 3ak突变体仍然可以维持昼夜节律并参与进食。
Pitx3ak mice lack a functioning retina and develop fewer than 10% of dopamine neurons in the substantia nigra. reported that entrainment of circadian rhythms to daily light-dark (LD) cycles is absent in these mice, and that rhythms of locomotor activity, energy expenditure, and other metabolic variables are disrupted with food available ad libitum and fail to entrain to a daily feeding. The authors propose that retinal innervation of the suprachiasmatic nucleus is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms in Pitx3ak mice do not entrain to LD cycles, but we find no impairment in circadian organization of metabolism with food available ad libitum and no impairment in entrainment of metabolic or behavioral rhythms by daily feeding schedules. This Matters Arising paper is in response to, published in Cell Reports. See also the response by, published in this issue. Scarpa et al. demonstrate that, despite what had been reported by, Pitxak mutant mice do indeed entrain behavior and metabolism to scheduled feeding. Key methodological differences between these studies are discussed, and long-term, calorie-restricted feeding conditions are essential for proper visualization of behavioral entrainment to scheduled feeding. It is remarkable that, despite having so few dopamine neurons in their substantia nigra and almost completely lacking lenses and retinal function, the Pitx3ak mutants can maintain circadian rhythms and entrain to feeding.
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