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

Janet Best; Ruby Kim; Michael Reed; H Frederik Nijhout

doi:10.1016/j.mbs.2024.109280

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

Math Biosci. 2024 Sep 6:377:109280. doi: 10.1016/j.mbs.2024.109280. Online ahead of print.

Authors

Janet Best¹, Ruby Kim², Michael Reed³, H Frederik Nijhout⁴

Affiliations

¹ Department of Mathematics, The Ohio State University, 231 W. 18th Ave., Columbus, 43210, OH, USA. Electronic address: best.82@osu.edu.
² Department of Mathematics, University of Michigan, 2074 East Hall, 530 Church St., Ann Arbor, 48109, MI, USA.
³ Department of Mathematics, Duke University, 120 Science Drive, Campus box 90338, Durham, 27708, NC, USA.
⁴ Department of Biology, Duke University, Biological Sciences Building, Campus box 90320, Durham, 27708, NC, USA.

PMID: 39243938
DOI: 10.1016/j.mbs.2024.109280

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.

Keywords: Circadian clock; Melatonin; Phase response curves; Serotonin.