Abstract
The growing importance of astrocytes in the field of neuroscience has led to a greater number of computational models devoted to the study of astrocytic functions and their metabolic interactions with neurons. The modeling of these interactions demands a combined understanding of brain physiology and the development of computational frameworks based on genomic-scale reconstructions, system biology, and dynamic models. These computational approaches have helped to highlight the neuroprotective mechanisms triggered by astrocytes and other glial cells, both under normal conditions and during neurodegenerative processes. In the present review, we evaluate some of the most relevant models of astrocyte metabolism, including genome-scale reconstructions and astrocyte-neuron interactions developed in the last few years. Additionally, we discuss novel strategies from the multi-omics perspective and computational models of other glial cell types that will increase our knowledge in brain metabolism and its association with neurodegenerative diseases.
Highlights
Astrocytes have gained a broad interest in neuroscience as they are essential for the maintenance of brain homeostasis and neuronal protection
The development of a comprehensive view of the astrocytic mechanisms involved in the brain-behavior requires a systemic approach, that can be assessed utilizing computational modelings, such as genome-scale metabolic models (GSMMs), which are created through an iterative process, integrating experimental evidence and computational approaches (Liu and Chen, 2010)
We focus on the current progress in computational models of astrocytic metabolism including genome-scale reconstructions, dynamical models, and multi-omic perspectives
Summary
Astrocytes have gained a broad interest in neuroscience as they are essential for the maintenance of brain homeostasis and neuronal protection. Gliotransmitter release is modulated through changes in the intracellular calcium concentration ([Ca2+]i) and the subsequent release of synaptic-like vesicles that involve a tightly controlled regulation mechanism (Harada et al, 2016) Many of these astrocytic features have been studied using computational models of different kinds (e.g., single-cell models, metabolic reconstructions, dynamic models) due to their importance for neuronal physiology and pathology (Figure 1). Due to the critical importance of astrocytes for brain homeostasis, neuronal protection, and metabolic regulation, there has been a growing interest in the study of astrocytic functions and metabolism through the use of computational tools, models and databases (Li et al, 2010; Volman et al, 2012; Linne and Jalonen, 2014; Sertbaset al., 2014; Oschmann et al, 2016; Martín-Jiménez et al, 2017; Manninen et al, 2018). With the advent of high-throughput technologies, it is possible to study brain metabolism from a systemic point of view that includes thousands of biochemical reactions with complex metabolic networks (Allaman et al, 2011; Bélanger et al, 2011)
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