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dc.creatorČupić, Željko
dc.creatorMarković, Vladimir M.
dc.creatorMacesic, Stevan
dc.creatorStanojevic, Ana
dc.creatorDamjanovic, Svetozar
dc.creatorVukojevic, Vladana
dc.creatorKolar-Anić, Ljiljana
dc.date.accessioned2019-01-30T17:52:08Z
dc.date.available2017-04-01
dc.date.issued2016
dc.identifier.issn1054-1500
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2036
dc.description.abstractDynamic 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.en
dc.publisherAmer Inst Physics, Melville
dc.relationKarolinska Institute Research Funds
dc.relationSwedish Research Council
dc.relationKnut and Alice Wallenberg Foundation
dc.relationRajko and Maj Dermanovic Fund
dc.relationCMST COST Action Emergence and Evolution of Complex Chemical Systems - CM1304
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172015/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/45001/RS//
dc.rightsembargoedAccess
dc.sourceChaos
dc.titleDynamic transitions in a model of the hypothalamic-pituitary-adrenal axisen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЧупић, Жељко; Марковиц, Владимир М; Колар-Aниц, Љиљана; Дамјановиц, Светозар; Мацесиц, Стеван; Станојевиц, Aна; Вукојевиц, Владана;
dc.citation.volume26
dc.citation.issue3
dc.citation.other26(3):
dc.citation.rankaM21
dc.identifier.pmid27036189
dc.identifier.doi10.1063/1.4944040
dc.identifier.rcubConv_3513
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs/bitstream/id/14453/Dynamic_transitions_in_a_model_of_the_hypothalamic.pdf
dc.identifier.scopus2-s2.0-85018356777
dc.identifier.wos000373644100012
dc.type.versionpublishedVersion


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