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

Mauro Di Nuzzo, Federico Giove, Bruno Maraviglia

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.

Keywords


Neurons, energy metabolism, lactate, dynamic mopdels.

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