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

Scientific Reports
Rohit Rao, Ioannis P Androulakis

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...Continue Reading

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Citations

Dec 20, 2020·Physiological Reports·Carol Jones, Christopher Gwenin
Jan 14, 2021·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Ioannis P Androulakis
Apr 1, 2021·Annual Review of Biomedical Engineering·Yaakov Nahmias, Ioannis P Androulakis

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