Modeling the Non-Linear Dynamics of Information Flows in Neuro-Endocrine Systems

Nonlinear feedback loops inherent to neuroendocrine systems are among the most important information flows at the organism level. They support high sensitivity and responsiveness of the living beings to external perturbations. Moreover, nonlinear feedback loops enable efficient control over dynamic physiological states. Often, they can be recognized through emergence of various dynamic phenomena, such as biological rhythmicity. Typical examples of such neuroendocrine systems are the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic–pituitary–thyroid (HPT) axis. They are characterized by rhythmic dynamics with two characteristic periods, circadian (~ 24 h) and ultradian (20 min – 120 min), which allows living organisms to quickly adjust their neuroendocrine activity to fluctuations in their surroundings and/or their internal physiology. We focus our research on mechanistic modelling of biochemical transformations that underlay complex neuroendocrine networks. Thus far, we have developed several variants of low-dimensional and extended models for the HPA axis, as well as, one medium scale model of the HPT axis. Both of them are assembled by combinations of the pseudo-reaction steps, describing in essence the information flow through the network of chemical transformations. Their role in physiological system is to maintain basal levels of hormone concentrations, and enable their functionally reasonable change when some need emerges. Our models enable one to emulate in numerical simulations changes in blood level of relevant hormones that constitute the HPA or HPT axis (Jelić et al. 2005, Marković et al. 2011, Čupić et al. 2017, Kolar-Anić et al. 2023). The high predictive value of our models paves the way for their use in medical diagnostics of neuroendocrine diseases and for more efficient corticosteroid treatment that is applied in various illnesses, by harnessing the power of the underlying nonlinear feedback loops to the dosage of corticosteroid drugs could be significantly decreased, while preserving their efficacy. We pay special attention to the Stoichiometric Network Analysis of reaction network models to identify conditions ensuring the existence of unstable steady states, and in particular, Hopf bifurcation as a most plausible path leading to the oscillatory dynamics. The simplest way to use this template is to replace the text in this file with your own words using the styles provided as far as possible

Bray-Liebhafsky reaction: From monotonous to chaotic evolution

Many physicochemical processes can exhibit various forms of non-linear dynamics, which have been widely investigated in the oscillatory reaction Bray-Liebhafsky, too. The stoichiometry of this reaction corresponds to the hydrogen peroxide decomposition to water and oxygen in an acidic environment, in the presence of iodate ions as a catalyst. During this reaction an oscillatory change of the intermediate species concentration, along with a cascade change in the hydrogen peroxide concentration and oxygen removal can be obtained. By selecting the experimental conditions, the simple periodic or complex chaotic concentration changes can be generated. Concentration oscillations are a consequence of alternating dominance of different reaction pathways present in the reaction mechanism. Large extent of the phenomena experimentally observed in the oscillatory reaction Bray- Liebhafsky is well explained by the mechanistic model, investigated by the Belgrade group over a many years

The influence of nafion on oxidation of glucose on gold electrode from alkaline solutions

The influence of Nafion on oxidation of glucose on gold electrode in 0.1 M NaOH solution was investigated. The presence of Nafion on the surface of gold electrode decreased the rate of glucose oxidation in alkaline solution. The mechanism of glucose oxidation is not changed by the presence of Nafion

Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin

An upgraded model of the Hypothalamic-Pituitary-Adrenal (HPA) axis has been developed that advances our previously proposed low-dimensional HPA model by including the effects of arginine vasopressin (AVP) that is a key modulator of HPA axis function. The upgraded model allows us to emulate AVP effects on HPA axis dynamics individually and in synergy with the corticotropin-releasing hormone (CRH). In this work, we examine how coupling of the circadian function through summarised reaction steps describing CRH and AVP biosynthesis in the same neuronal cell group of the hypothalamic paraventricular nucleus (PVN) affects HPA axis dynamics. Results of numerical simulations show that coupling of the circadian function through both, CRH and AVP summarised biosynthesis reaction steps simultaneously, emulates best the HPA axis dynamics, in line with literature findings

Various dinamical states in the Bray-Liebhafsky oscillatory reaction- from periodicity to intermittent chaos

The Bray-Liebhafsky (BL) is one of the most analyzed oscillatory reaction both experimentally and numerically. Most of the experimentally obtained dynamical states of this reaction realized in a continuously fed well stirred tank reactor (CSTR) are successfully simulated. Beside others, numerous structured chaotic dynamical states were obtained between each two periodic states in the period doubling rout to chaos with respect to specific flow rate as the control parameter. It was an universal scenario throughout the whole mixed-mode region, as well as throughout other mixed-mode regions obtained under different initial conditions. However, the intermittent oscillations consistent of chaotic mixture of large-amplitude relaxation oscillations, grouped in bursts and small-amplitude sinusoidal ones or even quiescent parts between them known as gaps were also generated experimentally in the Bray–Liebhafsky reaction by varying different parameters such as temperature, flow rate or reactant concentrations under CSTR conditions. Nevertheless, it will be shown here that intermittent oscillations can be simulated by already published model of the BL reaction network

Formation Of Hydroquinone And Catechol During Electrooxidation Of Phenol On Clay-Modified Electrodes

Clay was modified by pillaring, which was performed by combinations of pillaring cations: Al3+ and Fe3+ or Al3+, Fe3+ and Ni2+. The synthesized materials were used to obtain glassy carbon electrode (GCE) coatings. Electrochemical oxidation of phenol from acidic solution was investigated on clay-modified electrodes by method of cyclic voltammetry. As a consequence of electrode fouling the peak current registered in the tenth cycle droped in the comparison to the current obtained in the first cycle. The first-order derivative linear sweep voltammetry was used in the analytical procedure. Hydroquinone/catechol current ratio increased in the opposite manner to the phenol oxidation current drop

Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol

The previously proposed stoichiometric model of the Hypothalamic-Pituitary-Adrenal (HPA) axis activity that took into account arginine vasopressin (AVP), has been further developed to emulate ultradian oscillations of corticotropin-releasing hormone (CRH) and AVP. With this aim, additional coupling of HPA consisting hormones was introduced into this model by reaction between CRH and cortisol (CORT). How additional coupling of hormones affects HPA axis ultradian dynamics and reflects on ultradian oscillations of AVP and CRH concentrations was examined by using numerical simulations and bifurcation analysis. Results show that the rate constant of newly incorporated reaction alone is sufficient to be adjusted only for CRH to exhibit oscillations with optimally prominent amplitudes. Also, oscillation frequencies of CRH were found to be in accordance with findings in the literature under all investigated condition

Numerical simulations of the oscillatory dynamics in the Bray-Liebhafsky reaction perturbed by L-tyrosine

It is well known that almost all living or biological systems are naturally in the oscillatory dynamic states and can be considered as biochemical reaction systems. These oscillatory dynamic states can be caused by internal self-organized phenomena, but also by external periodic variations of temperature, light, food, or seasonal changes. The hypothalamic-pituitary-thyroid (HPT) axis is one such nonlinear system with feedback that is always in an oscillatory dynamic state and L-tyrosine is its main representative. The biological importance of L-tyrosine interactions with iodine species was the motivation for modelling of the oscillatory dynamics in the Bray-Liebhafsky (BL) reaction perturbed by L- tyrosine. Also, direct experimental investigation of metabolic processes in the human body is extremely complex to be done, and therefore any alternative approach is of great importance. Therefore, the BL reaction has the potential to be used as a model of the biological system due to certain characteristics shared with the considered processes; it is characterized by its oscillatory dynamics and based on the chemistry of hydrogen peroxide and iodine compounds commonly present in the thyroid gland, where L-tyrosine is iodinated. The impact of L-tyrosine on the dynamics of the Bray-Lienbhafsky oscillatory reaction was investigated numerically using the proposed model. The study was focused on the examination of the sensitivity of the BL reaction to L-tyrosine perturbation. The obtained results indicated possible pathways of influenc

L-tyrosine influence on the reaction kinetics of iodatehydrogen peroxide oscillatory reaction

The impact of L-tyrosine amino acid on the kinetics of the BL oscillatory reaction was investigated under closed reactor conditions. The study was focused on examining the sensitivity of the BL reaction matrix to tyrosine perturbations. A high sensitivity of the BL matrix to very low tyrosine concentrations was observed

Cyclic Voltammetric Study of the Influence of Porosity on Electrochemical Response of Nickel-Alumina Modified Glassy Carbon Electrode

Pure and nickel-modified alumina powders with different porosity were synthesized and applied on the glassy carbon electrode by means of Nafion polymer. The data obtained from the nitrogen adsorption-desorption isotherm confirmed that the pore structures in these materials are complex and tend to be made up of interconnected networks of pores of different size and shape. The addition of Ni2+ ions caused the changes in the textural properties of the samples. The influence of porosity on the electrochemical behavior of modified electrodes in quasi-reversible process was tested by cyclic voltammetry. Numerical correlations between electrochemical responses of GCE modified with alumina samples and textural properties have been established