Glucose metabolism and astrocyte–neuron interactions in the neonatal brain

•Glucose is essential for neonatal brain metabolism.•The pentose phosphate pathway is very active in neonatal brain.•Pyruvate carboxylation is important for glutamate synthesis.•Glutamine is transferred from astrocytes to neurons.•Not much neuronal glutamate is reaching astrocytes. Glucose is essentially the sole fuel for the adult brain and the mapping of its metabolism has been extensive in the adult but not in the neonatal brain, which is believed to rely mainly on ketone bodies for energy supply. However, glucose is absolutely indispensable for normal development and recent studies have shed light on glycolysis, the pentose phosphate pathway and metabolic interactions between astrocytes and neurons in the 7-day-old rat brain. Appropriately 13C labeled glucose was used to distinguish between glycolysis and the pentose phosphate pathway during development. Experiments using 13C labeled acetate provided insight into the GABA–glutamate–glutamine cycle between astrocytes and neurons. It could be shown that in the neonatal brain the part of this cycle that transfers glutamine from astrocytes to neurons is operating efficiently while, in contrast, little glutamate is shuttled from neurons to astrocytes. This lack of glutamate for glutamine synthesis is compensated for by anaplerosis via increased pyruvate carboxylation relative to that in the adult brain. Furthermore, compared to adults, relatively more glucose is prioritized to the pentose phosphate pathway than glycolysis and pyruvate dehydrogenase activity. The reported developmental differences in glucose metabolism and neurotransmitter synthesis may determine the ability of the brain at various ages to resist excitotoxic insults such as hypoxia-ischemia.