Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis
Marković, Vladimir M.
Article (Published version)
MetadataShow full item record
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., th...e 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.
Source:Chaos, 2016, 26, 3
- Amer Inst Physics, Melville
- Karolinska Institute Research Funds
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Rajko and Maj Dermanovic Fund
- CMST COST Action Emergence and Evolution of Complex Chemical Systems - CM1304
- Dynamics of nonlinear physicochemical and biochemical systems with modeling and predicting of their behavior under nonequilibrium conditions (RS-172015)
- Nanostructured Functional and Composite Materials in Catalytic and Sorption Processes (RS-45001)