TY  - JOUR
AU  - Stanojevic, Ana
AU  - Marković, Vladimir M.
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
AU  - Vukojevic, Vladana
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2365
AB  - Stress is a physiological reaction of an organism to a demand for change that is imposed by external factors or is coming from within by way of physiological strains or self-perceived mental and/or emotional threats (internal factors). It manifests itself through the sudden release of a flood of hormones, including corticosteroids, into the blood, which rouse the body for action. Normally, stress is beneficial, but when lasting or being very strong, it causes major damage to our mind and body. Despite intense research, we still do not understand fully how the stress response axis, whose main function is to respond to challenges while maintaining the normal physiological balance, loses under prolonged exposure to stressors its capacity to maintain homeostasis. Recent applications of mathematical modelling and dynamical systems theory have enabled us to emulate complex neurochemical transformations that underlie the stress response, and help us to acquire deeper understanding of this dynamical regulatory network.
PB  - Elsevier Sci Ltd, Oxford
T2  - Current Opinion in Chemical Engineering
T1  - Advances in mathematical modelling of the hypothalamic-pituitary-adrenal (HPA) axis dynamics and the neuroendocrine response to stress
VL  - 21
SP  - 84
EP  - 95
DO  - 10.1016/j.coche.2018.04.003
ER  - 

@article{
author = "Stanojevic, Ana and Marković, Vladimir M. and Čupić, Željko and Kolar-Anić, Ljiljana and Vukojevic, Vladana",
year = "2018",
abstract = "Stress is a physiological reaction of an organism to a demand for change that is imposed by external factors or is coming from within by way of physiological strains or self-perceived mental and/or emotional threats (internal factors). It manifests itself through the sudden release of a flood of hormones, including corticosteroids, into the blood, which rouse the body for action. Normally, stress is beneficial, but when lasting or being very strong, it causes major damage to our mind and body. Despite intense research, we still do not understand fully how the stress response axis, whose main function is to respond to challenges while maintaining the normal physiological balance, loses under prolonged exposure to stressors its capacity to maintain homeostasis. Recent applications of mathematical modelling and dynamical systems theory have enabled us to emulate complex neurochemical transformations that underlie the stress response, and help us to acquire deeper understanding of this dynamical regulatory network.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Current Opinion in Chemical Engineering",
title = "Advances in mathematical modelling of the hypothalamic-pituitary-adrenal (HPA) axis dynamics and the neuroendocrine response to stress",
volume = "21",
pages = "84-95",
doi = "10.1016/j.coche.2018.04.003"
}

Stanojevic, A., Marković, V. M., Čupić, Ž., Kolar-Anić, L.,& Vukojevic, V.. (2018). Advances in mathematical modelling of the hypothalamic-pituitary-adrenal (HPA) axis dynamics and the neuroendocrine response to stress. in Current Opinion in Chemical Engineering
Elsevier Sci Ltd, Oxford., 21, 84-95.
https://doi.org/10.1016/j.coche.2018.04.003

Stanojevic A, Marković VM, Čupić Ž, Kolar-Anić L, Vukojevic V. Advances in mathematical modelling of the hypothalamic-pituitary-adrenal (HPA) axis dynamics and the neuroendocrine response to stress. in Current Opinion in Chemical Engineering. 2018;21:84-95.
doi:10.1016/j.coche.2018.04.003 .

Stanojevic, Ana, Marković, Vladimir M., Čupić, Željko, Kolar-Anić, Ljiljana, Vukojevic, Vladana, "Advances in mathematical modelling of the hypothalamic-pituitary-adrenal (HPA) axis dynamics and the neuroendocrine response to stress" in Current Opinion in Chemical Engineering, 21 (2018):84-95,
https://doi.org/10.1016/j.coche.2018.04.003 . .

TY  - JOUR
AU  - Marković, Vladimir M.
AU  - Čupić, Željko
AU  - Macesic, Stevan
AU  - Stanojevic, Ana
AU  - Vukojevic, Vladana
AU  - Kolar-Anić, Ljiljana
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1929
AB  - A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.
PB  - Oxford Univ Press, Oxford
T2  - Mathematical Medicine and Biology-A Journal of the Ima
T1  - Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis
VL  - 33
IS  - 1
SP  - 1
EP  - 28
DO  - 10.1093/imammb/dqu020
ER  - 

@article{
author = "Marković, Vladimir M. and Čupić, Željko and Macesic, Stevan and Stanojevic, Ana and Vukojevic, Vladana and Kolar-Anić, Ljiljana",
year = "2016",
abstract = "A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.",
publisher = "Oxford Univ Press, Oxford",
journal = "Mathematical Medicine and Biology-A Journal of the Ima",
title = "Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis",
volume = "33",
number = "1",
pages = "1-28",
doi = "10.1093/imammb/dqu020"
}

Marković, V. M., Čupić, Ž., Macesic, S., Stanojevic, A., Vukojevic, V.,& Kolar-Anić, L.. (2016). Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis. in Mathematical Medicine and Biology-A Journal of the Ima
Oxford Univ Press, Oxford., 33(1), 1-28.
https://doi.org/10.1093/imammb/dqu020

Marković VM, Čupić Ž, Macesic S, Stanojevic A, Vukojevic V, Kolar-Anić L. Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis. in Mathematical Medicine and Biology-A Journal of the Ima. 2016;33(1):1-28.
doi:10.1093/imammb/dqu020 .

Marković, Vladimir M., Čupić, Željko, Macesic, Stevan, Stanojevic, Ana, Vukojevic, Vladana, Kolar-Anić, Ljiljana, "Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis" in Mathematical Medicine and Biology-A Journal of the Ima, 33, no. 1 (2016):1-28,
https://doi.org/10.1093/imammb/dqu020 . .

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 . .