A mathematical model of melatonin synthesis and interactions with the circadian clock

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Janet Best , Ruby Kim , Michael Reed , H. Frederik Nijhout
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Abstract

A new mathematical model of melatonin synthesis in pineal cells is created and connected to a slightly modified previously created model of the circadian clock in the suprachiasmatic nucleus (SCN). The SCN influences the production of melatonin by upregulating two key enzymes in the pineal. The melatonin produced enters the blood and the cerebrospinal fluid and thus the SCN, influencing the circadian clock. We show that the model of melatonin synthesis corresponds well with extant experimental data and responds similarly to clinical experiments on bright light in the middle of the night. Melatonin is widely used to treat jet lag and sleep disorders. We show how the feedback from the pineal to the SCN causes phase resetting of the circadian clock. Melatonin doses early in the evening advance the clock and doses late at night delay the clock with a dead zone in between where the phase of the clock does not change.

Abstract Image

褪黑激素合成及与昼夜节律钟相互作用的数学模型。
建立了松果体细胞合成褪黑激素的新数学模型,并将其与之前建立的昼夜节律钟模型稍作修改后连接起来。SCN 通过上调松果体中的两种关键酶来影响褪黑激素的产生。产生的褪黑激素进入血液和脑脊液,进而进入 SCN,影响昼夜节律表。我们的研究表明,褪黑激素合成模型与现有的实验数据十分吻合,并对半夜强光的临床实验做出了类似的反应。褪黑素被广泛用于治疗时差和睡眠障碍。我们展示了松果体对SCN的反馈如何导致昼夜节律表的相位重置。褪黑素剂量在傍晚较早时使时钟提前,在深夜较晚时使时钟延迟,在这两者之间有一个死区,时钟的相位不会发生变化。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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