Lactate involvement in neuron–glia metabolic interaction: 13C-NMR spectroscopy contribution

Glucose is commonly admitted to be the main substrate for brain energy requirement. However, it has been recently proposed that lactate, generated from glucose via glycolysis, would be the oxidative substrate for neurons, particularly during neuronal activation, according to a mechanism called the astrocyte–neuron lactate shuttle hypothesis (ANLSH) [Proc. Natl. Acad. Sci. USA 91 (1994) 10625]. In that mechanism, glutamate released in the synaptic cleft during brain activation is taken up by astrocytes. This uptake, via the glutamate/Na+ transporter, induces the entry of sodium, which is then excluded from the astrocytes via the Na+/K+ ATPase. This exclusion consumes ATP, which stimulates glycolysis and thus lactate formation in astrocytes. This lactate is then transferred to neurons where it is utilized as oxidative substrate. This review tries to gather the recent evidences that support this hypothesis and presents the contribution of NMR to this matter.