TY  - JOUR
AU  - Čupić, Željko
AU  - Marković, Vladimir M.
AU  - Macesic, Stevan
AU  - Stanojevic, Ana
AU  - Damjanovic, Svetozar
AU  - Vukojevic, Vladana
AU  - Kolar-Anić, Ljiljana
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2036
AB  - Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamicpituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.
PB  - Amer Inst Physics, Melville
T2  - Chaos
T1  - Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis
VL  - 26
IS  - 3
DO  - 10.1063/1.4944040
ER  - 

@article{
author = "Čupić, Željko and Marković, Vladimir M. and Macesic, Stevan and Stanojevic, Ana and Damjanovic, Svetozar and Vukojevic, Vladana and Kolar-Anić, Ljiljana",
year = "2016",
abstract = "Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamicpituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.",
publisher = "Amer Inst Physics, Melville",
journal = "Chaos",
title = "Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis",
volume = "26",
number = "3",
doi = "10.1063/1.4944040"
}

Čupić, Ž., Marković, V. M., Macesic, S., Stanojevic, A., Damjanovic, S., Vukojevic, V.,& Kolar-Anić, L.. (2016). Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis. in Chaos
Amer Inst Physics, Melville., 26(3).
https://doi.org/10.1063/1.4944040

Čupić Ž, Marković VM, Macesic S, Stanojevic A, Damjanovic S, Vukojevic V, Kolar-Anić L. Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis. in Chaos. 2016;26(3).
doi:10.1063/1.4944040 .

Čupić, Željko, Marković, Vladimir M., Macesic, Stevan, Stanojevic, Ana, Damjanovic, Svetozar, Vukojevic, Vladana, Kolar-Anić, Ljiljana, "Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis" in Chaos, 26, no. 3 (2016),
https://doi.org/10.1063/1.4944040 . .