Computational singular perturbation analysis of brain lactate metabolism


Autoři: Dimitris G. Patsatzis aff001;  Efstathios-Al. Tingas aff001;  Dimitris A. Goussis aff004;  S. Mani Sarathy aff001
Působiště autorů: King Abdullah University of Science and Technology (KAUST), Clean Combustion Research Center (CCRC), Thuwal, Saudi Arabia aff001;  Department of Mechanics, School of Applied Mathematics and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece aff002;  Perth College, University of the Highlands and Islands, Crieff Rd, Perth PH1 2NX, United Kingdom aff003;  Department of Mechanical Engineering, Khalifa University of Science, Technology and Research (KUSTAR), Abu Dhabi, United Arab Emirates aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226094

Souhrn

Lactate in the brain is considered an important fuel and signalling molecule for neuronal activity, especially during neuronal activation. Whether lactate is shuttled from astrocytes to neurons or from neurons to astrocytes leads to the contradictory Astrocyte to Neuron Lactate Shuttle (ANLS) or Neuron to Astrocyte Lactate Shuttle (NALS) hypotheses, both of which are supported by extensive, but indirect, experimental evidence. This work explores the conditions favouring development of ANLS or NALS phenomenon on the basis of a model that can simulate both by employing the two parameter sets proposed by Simpson et al. (J Cereb. Blood Flow Metab., 27:1766, 2007) and Mangia et al. (J of Neurochemistry, 109:55, 2009). As most mathematical models governing brain metabolism processes, this model is multi-scale in character due to the wide range of time scales characterizing its dynamics. Therefore, we utilize the Computational Singular Perturbation (CSP) algorithm, which has been used extensively in multi-scale systems of reactive flows and biological systems, to identify components of the system that (i) generate the characteristic time scale and the fast/slow dynamics, (ii) participate to the expressions that approximate the surfaces of equilibria that develop in phase space and (iii) control the evolution of the process within the established surfaces of equilibria. It is shown that a decisive factor on whether the ANLS or NALS configuration will develop during neuronal activation is whether the lactate transport between astrocytes and interstitium contributes to the fast dynamics or not. When it does, lactate is mainly generated in astrocytes and the ANLS hypothesis is realised, while when it doesn’t, lactate is mainly generated in neurons and the NALS hypothesis is realised. This scenario was tested in exercise conditions.

Klíčová slova:

Algorithms – Astrocytes – Evolutionary rate – Glucose – Glucose metabolism – Neurons – Reactants – Reaction dynamics


Zdroje

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104. Neophytou MK, Goussis DA, Mastorakos E, Britter RE. The conceptual development of a simple scale-adaptive reactive pollutant dispersion model. Atmospheric Environment. 2005;39(15):2787–94. doi: 10.1016/j.atmosenv.2004.12.025

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110. Michalaki LI, Goussis DA. Asymptotic analysis of a TMDD model: when a reaction contributes to the destruction of its product. Journal of mathematical biology. 2018:1–35.

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