A BIOCHEMICAL FRAMEWORK FOR MODELING THE FUNCTIONAL METABOLISM OF THE HUMAN BRAIN

Abstract

The existence of complex control mechanisms in the catabolism of molecules utilized for energy production forms the basis of the relationship between function and metabolic regulation. This is especially important in the brain, where numerous in vitro and in vivo experiments have lend support to the theory of the coupling between neuronal activity and energy metabolism, a view enlightened several decades ago and now consolidated. Notwithstanding, many details remained unresolved about the fate of nutrients within the brain parenchyma and the consequent exchanges of substances, particularly between neurons and astrocytes, whose involvement in the neurometabolic coupling is well established. Unfortunately, due to limited spatial and temporal resolution, the currently available experimental techniques do not allow specific measurements of cerebral metabolites in different cell types in situ. Therefore, the analysis of the incomplete experimental data requires the formulation and application of mathematical models. In this paper, we explore these theoretical accounts in the construction of a unified biochemical framework of supply and demand in the context of compartmentalized brain energy metabolism. The model successfully predicts the time-course of observable variables, while providing information about a number of processes underlying neural activity. Future work is expected to gain insights by testing the model with respect to different hypotheses about transport and metabolic cell specialization, as well as about the degree of activation of neurons and astrocytes following brain stimulation.