Modelling of Neural Metabolism Using 13C-NMR Spectroscopy and Metabolic Flux Analysis

A metabolic flux analysis (MFA) study was performed to infer about the metabolic plasticity of astrocytes when exposed to two environmental stresses. In the first study an astrocytic culture was subjected to a hypoglycemic period of 24 h and the metabolic response was investigated during and after the insult. The second study involved another astrocytic culture that was subjected to an anoxic episode of three hours; and the metabolism was evaluated both before/during anoxia and in the recovery period (normal O2 levels re-established). In both studies [1-13C]glucose was administrated to the cultures and the incorporation of the label into metabolites was analysed by nuclear magnetic resonance (NMR) spectroscopy, allowing the assessment of particular pathways used by astrocytes. The oxidative metabolism of astrocytes exposed to hypoglycaemia increased during the recovery phase since an increase in tricarboxylic acid (TCA) cycle fluxes was observed. During anoxia, astrocytes respond by up-regulating their glycolytic capacity in order to maintain their energy requirements. When the O2 levels were restored, a metabolic shift towards a more oxidative utilization of glucose was observed when compared to pre-anoxic conditions.