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Exploring dynamics within the neuroendocrine-immune system

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POKOJSKÁ Eva

Rok publikování 2003
Druh Článek ve sborníku
Konference 6th IBRO World Congress of Neuroscience
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Klíčová slova regulatory network; model; neuroendocrine; immune; corticoids
Popis Depression, sleeping disorders, cognitive impairment, changes in water metabolism and resulting higher stroke risk or migraine appearance, and shifts in immune response are symptoms related to dysregulation of the hypothalamo-pituitary-adrenal axis (HPA). Previous studies point to releasing patterns of corticotropin releasing hormone (CRH) and their relations to autonomous neural system and hippocampal activity. As steroids, or melatonin can influence the feedbacks to HPA axis, changing the usual release patterns of CRH, we can consider above symptoms as side-effects of chronic steroid administration. In this work we want to reveal the interactions among various mediators forming the multiple inputs important for a fine modulation the specific mediator-release patterns. To present the dynamics in the regulatory system we introduce a method for grouping fairly homologous mediators to elucidate the regulational hierarchy conserved in humans. The method considers features of the appropriate signal transduction path, namely a structure of mediator, receptor, and a type of related downstream pathway. Based on the qualitative data on mediator production/ release after the neighbour mediator input signal, we have sketched particular metabolic sub-systems considering all feedbacks present. After replacing particular mediators in the sub-systems by their group-representatives it becomes clear that the between-groups interactions are either same for the metabolic sub-systems, or absent. Regarding the mediators grouping and the general rules for regulational hierarchy levels interactions we have designed a general scheme representing types of mediator - target cell interactions. Using discretization for the time evolution and mediator production/ release levels we implement a method of rule-based formalism theory. Our model wants to mimic the physiological regulation dynamics in the complex mediator system and simulate the changes under chronic steroid administration.
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