Aerobic glycolysis in the primate brain: reconsidering the implications for growth and maintenance

Glucose metabolism produces, by oxidative phosphorylation, more than 15 times the amount of energy generated by aerobic glycolysis. Nonetheless, aerobic glycolysis remains a prevalent metabolic pathway in the brain. Here we review evidence suggesting that this pathway contributes essential molecules to the biomass of the brain. Aerobic metabolism is the dominant metabolic pathway during early postnatal development when lipids and proteins are needed for the processes of axonal elongation, synaptogenesis, and myelination. Furthermore, aerobic metabolism may continue into adulthood to supply biomolecules for activity-related changes at the synapse and turnover of constituent structural components of neurons. Conversely, oxidative phosphorylation appears to be the main metabolic support for synaptic transmission, and, therefore, this pathway seems to be more dominant in brain structures and at time points in the lifespan that are characterized by increased synaptic density. We present the case for differing relationships between aerobic glycolysis and oxidative phosphorylation across primates in association with species-specific variation in neurodevelopmental trajectories. In doing so, we provide an alternative interpretation for the assessment of radiolabeled glucose positron emission tomography studies that regularly attribute increases in glucose uptake to neural activity alone, and propose a new model for the contribution of metabolic pathways for energetic demand and neural tissue growth. We conclude that comparative studies of metabolic appropriation in the brain may contribute to the discussion of human cognitive evolution and to the understanding of human-specific aging and the etiology of neuropsychiatric diseases.