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缺乏 Bmal1 会导致节律变化,并损害对自然刺激的动机。

Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli.

机构信息

Department of Medicine and Life Sciences (MELIS), Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Universitat Pompeu Fabra, Barcelona, Spain.

Department of Medicine and Life Sciences (MELIS), Synthetic Biology for Biomedical Applications, Universitat Pompeu Fabra, Barcelona, Spain.

出版信息

Open Biol. 2024 Jul;14(7):240051. doi: 10.1098/rsob.240051. Epub 2024 Jul 24.

Abstract

Maintaining proper circadian rhythms is essential for coordinating biological functions in mammals. This study investigates the effects of daily arrhythmicity using Bmal1-knockout (KO) mice as a model, aiming to understand behavioural and motivational implications. By employing a new mathematical analysis based on entropy divergence, we identified disrupted intricate activity patterns in mice derived by the complete absence of BMAL1 and quantified the difference regarding the activity oscillation's complexity. Changes in locomotor activity coincided with disturbances in circadian gene expression patterns. Additionally, we found a dysregulated gene expression profile particularly in brain nuclei like the ventral striatum, impacting genes related to reward and motivation. Further investigation revealed that arrhythmic mice exhibited heightened motivation for food and water rewards, indicating a link between circadian disruptions and the reward system. This research sheds light on how circadian clock alterations impact the gene expression regulating the reward system and how this, in turn, can lead to altered seeking behaviour and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.

摘要

维持适当的昼夜节律对于协调哺乳动物的生物功能至关重要。本研究以 Bmal1 基因敲除(KO)小鼠为模型,探讨了日常节律紊乱的影响,旨在了解行为和动机的影响。通过采用一种基于熵散度的新数学分析方法,我们发现完全缺乏 BMAL1 的小鼠的活动模式出现了紊乱,并对活动振荡复杂性的差异进行了量化。运动活动的变化与昼夜节律基因表达模式的紊乱相吻合。此外,我们还发现了一些特定于脑核(如腹侧纹状体)的基因表达谱的失调,这些基因与奖励和动机有关。进一步的研究表明,节律紊乱的小鼠对食物和水奖励的动机增强,表明昼夜节律紊乱与奖励系统之间存在联系。这项研究揭示了昼夜节律钟改变如何影响调节奖励系统的基因表达,以及这反过来如何导致对自然奖励的寻求行为和动机的改变。总之,本研究有助于我们理解奖励处理是如何受到昼夜节律钟机制调节的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad9/11267724/5b239d068e6c/rsob.240051.f001.jpg

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