Uncertainty quantification in flux balance analysis of spatially lumped and distributed models of neuron-astrocyte metabolism
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Publication:338375
DOI10.1007/S00285-016-1011-7zbMATH Open1350.92006arXiv1412.5693OpenAlexW2346632912WikidataQ48768537 ScholiaQ48768537MaRDI QIDQ338375FDOQ338375
Erkki Somersalo, Yougan Cheng, Daniela Calvetti
Publication date: 4 November 2016
Published in: Journal of Mathematical Biology (Search for Journal in Brave)
Abstract: The degrees of freedom of multi-compartment mathematical models for energy metabolism of a neuron-astrocyte complex may offer a key to understand the different ways in which the energetic needs of the brain are met. In this paper we address the problem within a steady state framework and we use the techniques of linear algebra to identify the degrees of freedom first in a lumped model, then in its extension to a spatially distributed case. The interpretation of the degrees of freedom in metabolic terms, more specifically in terms of glucose and oxygen partitioning, is then leveraged to derive constraints on the free parameters needed to guarantee that the model is energetically feasible. We also demonstrate how the model can be used to estimate the stoichiometric energy needs of the cells as well as the household energy based on observed oxidative cerebral metabolic rate (CMR) of glucose, and the glutamate cycling. Moreover, our analysis shows that in the lumped model the direction of lactate dehydrogenase (LDH) in the cells can be deduced from the glucose partitioning between the compartments. The extension of the lumped model into a spatially distributed multi-compartment setting that includes diffusion fluxes from capillary to tissue increases the number of degrees of freedom, requiring the use of statistical sampling techniques. The analysis of distributed model reveals that some of the conclusions, e.g., concerning the LDH activity and glucose partitioning, based on a spatially lumped model may no longer hold.
Full work available at URL: https://arxiv.org/abs/1412.5693
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Cites Work
- Introduction to Bayesian Scientific Computing
- A spatially distributed computational model of brain cellular metabolism
- Monte Carlo sampling can be used to determine the size and shape of the steady-state flux space
- Dynamic activation model for a glutamatergic neurovascular unit
- Bayesian stationary state flux balance analysis for a skeletal muscle metabolic model
Cited In (4)
- A spatially distributed computational model of brain cellular metabolism
- A spatially distributed model of brain metabolism highlights the role of diffusion in brain energy metabolism
- Multiscale Flux-Based Modeling of Biofilm Communities
- A computational model integrating brain electrophysiology and metabolism highlights the key role of extracellular potassium and oxygen
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