Computacional analysis of intracellular calcium elevations related to morphology changes in astrocytes

Abstract

Astrocytes, an essential type of glial cells, seem to be part of many neuropathologies, such as in Alzheimer's, where the astrocyte's soma and processes swells up. Astrocytes use intracellular calcium (Ca2+) elevations to encode information and generate main functional chores of the cell. The increase of the astrocytic Ca2+ levels could be related to the synaptic activity in the brain. There is a lack of understanding of the detailed spatiotemporal Ca2+ dynamics in astrocytes, and computational modeling can help us to comprehend this phenomenon better. In this work, we will study how morphological changes in the astrocytes affect their intracellular Ca2+ . This thesis proposes a 2D single-cell astrocyte model, simulated with the finite elements method (FEM) in COMSOL Multiphysics based on the previous study by Khalid et al. (2018). The mathematical model that describes the IP3 and calcium phenomena is based on the model by De Pittà et al. (2009). This model was implanted in FEM and extended to cover the diffusion inside the astrocyte. Additionally, the influence of four different Ca2+ buffering models was examined. MATLAB and Minitab softwares were used for analyzing the data. Two different geometrical models were evaluated in order to analyse the influence of different geometrical parameters as the thickness of a process, the angle between subprocesses or the stimulus distribution to the calcium behaviour in the astrocyte. The results showed that the frequency and propagation distance of the Ca2+ events are higher in narrow processes compared to wider ones while having the same stimulus. Also, my analysis showed that the angle between subprocesses and the stimulus distribution does not significantly affect the Ca2+ events, suggesting a possibility to to simplify future geometries. Finally, promising results showed the significant influence of the local geometry and the possibility of clustering the data by the geometrical shape. It has been statically proved how the distance between clusters is more significant when the astrocyte geometries present bigger differences between them. Furthermore, the Ca2+ buffers were studied, and the intracellular Ca2+ was affected differently depending on the buffering model, parameters, and complexity. This work forms a base for the analysis of the Ca2+ in astrocytes. It also improves our understanding of the impact of morphological changes in Ca2+ signaling, like the thickening of astrocyte processes in different pathologies.