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For decades, generations of researchers have encountered the paradox of aerobic glycolysis after neuronal activity, a process that would involve producing energy less efficiently than is actually required. In recent years, the CECs Biology Lab has focused on examining this process and understanding how brain cells manage to maintain their energy level during the great changes in demand that characterize them. In this way, an important advance in this line of research is achieved, which was reported in the Proceedings of the National Academy of Sciences of USA, this is the identification of a molecular mechanism that allows neurons to obtain oxygen by inhibiting the breathing of their astrocytes neighbors.


Astrocytes are cells that are more abundant in the human brain than neurons, these perform the dual task of generating and distributing energy blocks for neurons, a process known as neurometabolic coupling. One of the mysteries that has persisted for decades, is that although neuronal activity demands a lot of energy, this activity is accompanied by partial oxidation of glucose to lactate, rather than complete oxidation to CO2. Since oxygen is not lacking and total oxidation would generate 15 times more energy than partial oxidation, this phenomenon called aerobic glycolysis is a paradox.


Using advanced fluorescent imaging techniques, researchers found that neurons instruct astrocytes to turn on their aerobic glycolysis and at the same time turn off their mitochondrial respiration, a resource similar to that used by some tumor cells and yeast: The Crabtree effect. Aerobic glycolysis in the brain can then be understood as a strategy to redistribute oxygen to where it is most needed.


The work highlights the emerging role of astrocytes in brain function, broadening the concept of neurometabolic coupling by showing that astrocytes not only deliver glucose and lactate to the neurons, but also oxygen, thus ensuring information processing. The new mechanism also makes it possible to interpret the observations of Marcus Raichle's group on aerobic glycolysis in humans. As we age, our brain loses its ability to turn on aerobic glycolysis, a process similar to that seen in the early stages of Alzheimer's disease and other neurodegenerative diseases.




Ignacio Fernández, CECs Biology Laboratory researcher and lead author of the study, he was recently awarded the prestigious EMBO (European Molecular Biology Organization) grant, which will enable him to continue his postdoctoral studies in France.




Ref.: Aerobic glycolysis controls glial respiration. Ignacio Fernández-Moncada, Iván Ruminot, Daniel Robles-Maldonado, Karin Alegría, Joachim W. Deitmer, L. Felipe Barros Proceedings of the National Academy of Sciences Feb 2018, 115 (7) 1623-1628; DOI: 10.1073/pnas.1716469115