Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag

Abstract The suprachiasmatic nucleus (SCN) functions as the central pacemaker aligning physiological and behavioral oscillations to day/night (activity/inactivity) transitions. The light signal entrains the molecular clock of the photo-sensitive ventrolateral (VL) core of the SCN which in turn entra...

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Autores principales:	Yannuo Li, Ioannis P. Androulakis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c937539cc654ee7b5729f9fcf3ad12d
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spelling	oai:doaj.org-article:5c937539cc654ee7b5729f9fcf3ad12d2021-12-02T17:19:14ZLight entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag10.1038/s41598-021-97019-72045-2322https://doaj.org/article/5c937539cc654ee7b5729f9fcf3ad12d2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97019-7https://doaj.org/toc/2045-2322Abstract The suprachiasmatic nucleus (SCN) functions as the central pacemaker aligning physiological and behavioral oscillations to day/night (activity/inactivity) transitions. The light signal entrains the molecular clock of the photo-sensitive ventrolateral (VL) core of the SCN which in turn entrains the dorsomedial (DM) shell via the neurotransmitter vasoactive intestinal polypeptide (VIP). The shell converts the VIP rhythmic signals to circadian oscillations of arginine vasopressin (AVP), which eventually act as a neurotransmitter signal entraining the hypothalamic–pituitary–adrenal (HPA) axis, leading to robust circadian secretion of glucocorticoids. In this work, we discuss a semi-mechanistic mathematical model that reflects the essential hierarchical structure of the photic signal transduction from the SCN to the HPA axis. By incorporating the interactions across the core, the shell, and the HPA axis, we investigate how these coupled systems synchronize leading to robust circadian oscillations. Our model predicts the existence of personalized synchronization strategies that enable the maintenance of homeostatic rhythms while allowing for differential responses to transient and permanent light schedule changes. We simulated different behavioral situations leading to perturbed rhythmicity, performed a detailed computational analysis of the dynamic response of the system under varying light schedules, and determined that (1) significant interindividual diversity and flexibility characterize adaptation to varying light schedules; (2) an individual’s tolerances to jet lag and alternating shift work are positively correlated, while the tolerances to jet lag and transient shift work are negatively correlated, which indicates trade-offs in an individual’s ability to maintain physiological rhythmicity; (3) weak light sensitivity leads to the reduction of circadian flexibility, implying that light therapy can be a potential approach to address shift work and jet lag related disorders. Finally, we developed a map of the impact of the synchronization within the SCN and between the SCN and the HPA axis as it relates to the emergence of circadian flexibility.Yannuo LiIoannis P. AndroulakisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yannuo Li Ioannis P. Androulakis Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
description	Abstract The suprachiasmatic nucleus (SCN) functions as the central pacemaker aligning physiological and behavioral oscillations to day/night (activity/inactivity) transitions. The light signal entrains the molecular clock of the photo-sensitive ventrolateral (VL) core of the SCN which in turn entrains the dorsomedial (DM) shell via the neurotransmitter vasoactive intestinal polypeptide (VIP). The shell converts the VIP rhythmic signals to circadian oscillations of arginine vasopressin (AVP), which eventually act as a neurotransmitter signal entraining the hypothalamic–pituitary–adrenal (HPA) axis, leading to robust circadian secretion of glucocorticoids. In this work, we discuss a semi-mechanistic mathematical model that reflects the essential hierarchical structure of the photic signal transduction from the SCN to the HPA axis. By incorporating the interactions across the core, the shell, and the HPA axis, we investigate how these coupled systems synchronize leading to robust circadian oscillations. Our model predicts the existence of personalized synchronization strategies that enable the maintenance of homeostatic rhythms while allowing for differential responses to transient and permanent light schedule changes. We simulated different behavioral situations leading to perturbed rhythmicity, performed a detailed computational analysis of the dynamic response of the system under varying light schedules, and determined that (1) significant interindividual diversity and flexibility characterize adaptation to varying light schedules; (2) an individual’s tolerances to jet lag and alternating shift work are positively correlated, while the tolerances to jet lag and transient shift work are negatively correlated, which indicates trade-offs in an individual’s ability to maintain physiological rhythmicity; (3) weak light sensitivity leads to the reduction of circadian flexibility, implying that light therapy can be a potential approach to address shift work and jet lag related disorders. Finally, we developed a map of the impact of the synchronization within the SCN and between the SCN and the HPA axis as it relates to the emergence of circadian flexibility.
format	article
author	Yannuo Li Ioannis P. Androulakis
author_facet	Yannuo Li Ioannis P. Androulakis
author_sort	Yannuo Li
title	Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
title_short	Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
title_full	Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
title_fullStr	Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
title_full_unstemmed	Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
title_sort	light entrainment of the scn circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5c937539cc654ee7b5729f9fcf3ad12d
work_keys_str_mv	AT yannuoli lightentrainmentofthescncircadianclockandimplicationsforpersonalizedalterationsofcorticosteronerhythmsinshiftworkandjetlag AT ioannispandroulakis lightentrainmentofthescncircadianclockandimplicationsforpersonalizedalterationsofcorticosteronerhythmsinshiftworkandjetlag
_version_	1718381088291684352

Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag

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