Brain Metabolic Compartmentalization, Metabolism Modeling, and Cerebral Activity-Metabolism Relationship

Abstract

Brain metabolism modeling is a powerful method for analyzing ­pre-steady-state and steady-state kinetics of 13C incorporation in brain metabolites resulting from consumption of 13C-labeled substrates. Studies on brain metabolism modeling were initially carried out by considering a simple one-compartment model to analyze glutamate C4 labeling from [1-13C]glucose consumption. Thereafter, more sophisticated models including two or three compartments were used to analyze labeling of Glu, Gln, Asp and GABA at different carbon positions. In this chapter, after a brief recall of the cellular and molecular basis of brain metabolic compartmentalization, a survey of the metabolic pathways involved in the different models is presented. The discussion focuses on both the pathways generally considered in the modeling and those which are generally not considered, although ­evidence for their occurrence has been reported. Thereafter, the cerebral activity-metabolism relationship is analyzed through a review of the flux rates determined in rat brain under different cerebral activity status. More particularly, the relations between neuronal oxidative metabolism, glutamate-glutamine cycle, astrocytic oxidative metabolism and anaplerosis with cerebral activity are discussed. Some aspects concerning the reliability, the limitations and possible progress in brain metabolism modeling are finally discussed.