Modeling the functional network of primary intercellular Ca^2+ wave propagation in astrocytes and its application to study drug effects

DOI10.1016/J.JTBI.2014.04.024MaRDI QIDQ2415580zbMATH OpenOpenAlexWikidataFDO

Authors Frank Raischel, Sandra H. Vaz, Andreia Cruz-Silva, Ana M. Sebastião, Pedro G. Lind, Marcelo A. Pires

Publication date 23 May 2019

Published in Journal of Theoretical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1311.6965

zbMATH Keywords

complex networkssignal propagationcellular tissuesdrug tests

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Systems biology, networks (92C42)

Abstract: We introduce a simple procedure of multivariate signal analysis to uncover the functional connectivity among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based on the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance, one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude whether pairs of cells are functionally connected and in which direction. After testing the method against synthetic data we apply it to study intercellular propagation of Ca${}^{2+}$ waves in astrocytes following an external stimulus, with the aim of uncovering the functional cellular connectivity network. Our method proves to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based the statistical analysis of the connection weight distribution, we propose simple measures for assessing the impact of drugs on the functional connectivity between cells.

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Cites work

• scientific article; zbMATH DE number 3841211 (Why is no real title available?)
• scientific article; zbMATH DE number 2203240 (Why is no real title available?)
• scientific article; zbMATH DE number 3208729 (Why is no real title available?)
• Investigating Causal Relations by Econometric Models and Cross-spectral Methods

Cited in

(4)

• A new real-time analog circuit of Ca\(^{2+}\) Li-Rinzel astrocyte model based on analytical method
• A model for Ca\(^{2+}\) waves in networks of glial cells incorporating both intercellular and extracellular communication pathways
• A mathematical model of spontaneous calcium(II) oscillations in astrocytes
• A theoretical study on the role of astrocytic activity in neuronal hyperexcitability by a novel neuron-glia mass model

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