A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy.

Cardiovascular diseases associated with high cholesterol (hypercholesterolemia) and low-density lipoproteins (LDL) levels are significant contributors to total mortality in developing and developed countries. Mathematical modeling of LDL metabolism is an important step in the development of drugs for hypercholesterolemia. The aim of this work was to develop and to analyze an integrated mathematical model of cholesterol metabolism in liver cells and its interaction with two types of drugs, statins and PCSK9 inhibitors. The model consisted of 21 ordinary differential equations (ODE) describing cholesterol biosynthesis and lipoprotein endocytosis in liver cells in vitro. The model was tested for its ability to mimic known biochemical effects of familial hypercholesterolemia, statin therapy, and PCSK9 inhibitors. The model qualitatively reproduced the well-known biology of cholesterol regulation, which confirms its potential for minimizing cellular research in initial testing of new drugs for cardiology.

Astrocyte as Spatiotemporal Integrating Detector of Neuronal Activity.

The functional role of astrocyte calcium signaling in brain information processing was intensely debated in recent decades. This interest was motivated by high resolution imaging techniques showing highly developed structure of distal astrocyte processes. Another point was the evidence of bi-directional astrocytic regulation of neuronal activity. To analyze the effects of interplay of calcium signals in processes and in soma mediating correlations between local signals and the cell-level response of the astrocyte we proposed spatially extended model of the astrocyte calcium dynamics. Specifically, we investigated how spatiotemporal properties of Ca2+ dynamics in spatially extended astrocyte model can coordinate (e.g., synchronize) networks of neurons and synapses.

Astrocyte-induced positive integrated information in neuron-astrocyte ensembles.

Integrated information is a quantitative measure from information theory of how tightly all parts of a system are interconnected in terms of information exchange. In this study we show that astrocytes, playing an important role in regulation of information transmission between neurons, may contribute to a generation of positive integrated information in neuronal ensembles. Analytically and numerically we show that the presence of astrocytic regulation of neurotransmission may be essential for this information attribute in neuroastrocytic ensembles. Moreover, the proposed "spiking-bursting" mechanism of generating positive integrated information is shown to be generic and not limited to neuron-astrocyte networks and is given a complete analytic description.