Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach

Abstract The hypothalamic-pituitary-adrenal (HPA) axis orchestrates the physiological response to unpredictable acute stressors. Moreover, the HPA axis exhibits prominent circadian activity and synchronizes peripheral circadian clocks to daily environmental cycles, thereby promoting homeostasis. Per...

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Autores principales:	Rohit Rao, Ioannis P. Androulakis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/22b48df5cb5d48039ee82b134663b845
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spelling	oai:doaj.org-article:22b48df5cb5d48039ee82b134663b8452021-12-02T15:09:22ZAllostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach10.1038/s41598-019-47605-72045-2322https://doaj.org/article/22b48df5cb5d48039ee82b134663b8452019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47605-7https://doaj.org/toc/2045-2322Abstract The hypothalamic-pituitary-adrenal (HPA) axis orchestrates the physiological response to unpredictable acute stressors. Moreover, the HPA axis exhibits prominent circadian activity and synchronizes peripheral circadian clocks to daily environmental cycles, thereby promoting homeostasis. Persistent disruption of homeostatic glucocorticoid circadian rhythmicity due to chronic stress exposure is correlated with the incidence of various pathological conditions including depression, diabetes and cancer. Allostatic habituation of the HPA axis, such that glucocorticoid levels retain homeostatic levels upon chronic exposure to stress, can therefore confer fitness advantages by preventing the sustained dysregulation of glucocorticoid-responsive signaling pathways. However, such allostatic adaptation results in a physiological cost (allostatic load) that might impair the homeostatic stress-responsive and synchronizing functions of the HPA axis. We use mathematical modeling to characterize specific chronic stress-induced allostatic adaptations in the HPA network. We predict the existence of multiple individualized regulatory strategies enabling the maintenance of homeostatic glucocorticoid rhythms, while allowing for flexible HPA response characteristics. We show that this regulatory variability produces a trade-off between the stress-responsive and time-keeping properties of the HPA axis. Finally, allostatic regulatory adaptations are predicted to cause a time-of-day dependent sensitization of the acute stress response and impair the entrainability of the HPA axis.Rohit RaoIoannis P. AndroulakisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-15 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rohit Rao Ioannis P. Androulakis Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach
description	Abstract The hypothalamic-pituitary-adrenal (HPA) axis orchestrates the physiological response to unpredictable acute stressors. Moreover, the HPA axis exhibits prominent circadian activity and synchronizes peripheral circadian clocks to daily environmental cycles, thereby promoting homeostasis. Persistent disruption of homeostatic glucocorticoid circadian rhythmicity due to chronic stress exposure is correlated with the incidence of various pathological conditions including depression, diabetes and cancer. Allostatic habituation of the HPA axis, such that glucocorticoid levels retain homeostatic levels upon chronic exposure to stress, can therefore confer fitness advantages by preventing the sustained dysregulation of glucocorticoid-responsive signaling pathways. However, such allostatic adaptation results in a physiological cost (allostatic load) that might impair the homeostatic stress-responsive and synchronizing functions of the HPA axis. We use mathematical modeling to characterize specific chronic stress-induced allostatic adaptations in the HPA network. We predict the existence of multiple individualized regulatory strategies enabling the maintenance of homeostatic glucocorticoid rhythms, while allowing for flexible HPA response characteristics. We show that this regulatory variability produces a trade-off between the stress-responsive and time-keeping properties of the HPA axis. Finally, allostatic regulatory adaptations are predicted to cause a time-of-day dependent sensitization of the acute stress response and impair the entrainability of the HPA axis.
format	article
author	Rohit Rao Ioannis P. Androulakis
author_facet	Rohit Rao Ioannis P. Androulakis
author_sort	Rohit Rao
title	Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach
title_short	Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach
title_full	Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach
title_fullStr	Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach
title_full_unstemmed	Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach
title_sort	allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the hpa axis: a mathematical modeling approach
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/22b48df5cb5d48039ee82b134663b845
work_keys_str_mv	AT rohitrao allostaticadaptationandpersonalizedphysiologicaltradeoffsinthecircadianregulationofthehpaaxisamathematicalmodelingapproach AT ioannispandroulakis allostaticadaptationandpersonalizedphysiologicaltradeoffsinthecircadianregulationofthehpaaxisamathematicalmodelingapproach
_version_	1718387800038965248

Allostatic adaptation and personalized physiological trade-offs in the circadian regulation of the HPA axis: A mathematical modeling approach

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