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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

Authors

Dimitris Patsatzis

Mani Sarathy

Dimitris Goussis

Renaud Jolivet



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.

Presentation Conference Type Conference Paper (unpublished)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