Identification of Key Processes and Periods in a Model of Human Brain Energy Metabolism by Algorithmic Decomposition with Computational Singular Perturbation

Patsatzis, Dimitris; Tingas, Stathis; Sarathy, Mani; Goussis, Dimitris; Jolivet, Renaud

Abstract

Energetic considerations play a crucial role in brain function and disease. The study of brainenergy metabolism is, however, rendered difficult by a relative lack of experimental tools thatcan probe the contributions of different intricately connected cell types and processes. Inthis context, mathematical modelling has a role to play, but typically leads to models, whosecomplexity reflects that of the underlying biological system, and from which it is difficult toextract biologically actionable information.Here, an experimentally-calibrated multi-scale model of human brain energy metabolism [1] is analysed using the so-called Computational Singular Perturbation algorithm in order to identify key biological processes and periods, during and after a brain area has been activated. We identify a key role for both oxidative and glycolytic astrocytic metabolism in driving the behaviour of the brain's metabolic circuitry. Neuronal energy metabolism, by opposition, only plays a transient role for the first few seconds after the onset or offset of activation. We additionally identify a key role for the creatine phosphate shuttle in late stages of activation and post-activation. Our approach highlights the importance of glial cells in brain circuits, and introduces a systematic and unbiased methodology to study the dynamics of complex biochemical networks that can be readily scaled to metabolic networks of any size and complexity.

Citation

Patsatzis, D., Tingas, S., Sarathy, M., Goussis, D., & Jolivet, R. (2021, July). Identification of Key Processes and Periods in a Model of Human Brain Energy Metabolism by Algorithmic Decomposition with Computational Singular Perturbation. Paper presented at XV European Meeting on Glial Cells in Health and Disease, Online

• Presentation Conference Type: Conference Paper (unpublished)
• Conference Name: XV European Meeting on Glial Cells in Health and Disease
• Start Date: Jul 5, 2021
• End Date: Jul 9, 2021
• Deposit Date: Jan 24, 2022
• Public URL: http://researchrepository.napier.ac.uk/Output/2837028
• Publisher URL: https://onlinelibrary.wiley.com/toc/10981136/2021/69/S1