Compartmentalization of brain energy metabolism between glia and neurons: insights from mathematical modeling.

We review the contribution of mathematical modeling of metabolic pathways to the study of the compartmentalization of brain energy metabolism between neurons and glia. We especially focus on the role of lactate in the relationship between glia and neurons and the possible presence of an astrocyte-neuron lactate shuttle (ANLS). We first discuss models of glucose, pyruvate, and lactate kinetics, which are relevant to neuron-glia interactions. We then review models of compartmentalized energy metabolism, which deal with the concepts of 'red' and 'white' stimulations, and the ANLS hypothesis. We next show the contribution of a study of model robustness to the debate about the potential role of lactate in metabolic interactions between glia and neurons. Finally, we discuss the possible implications of modeling for further experimental studies.