Embracing the Modern Biochemistry of Brain Metabolism

Juan P Bolaños¹, Cristina M Alberini², Angeles Almeida¹, L Felipe Barros³, Gilles Bonvento⁴, Anne-Karine Bouzier-Sore⁵, Ralf Dringen⁶, Giles E Hardingham⁷, Johannes Hirrlinger^{8

9}, Pierre J Magistretti¹⁰, Giovanni Marsicano¹¹, Klaus-Armin Nave⁹, Rosa C Paolicelli¹², Luc Pellerin¹³, Pierre-Yves Plaçais¹⁴, Thomas Preat¹⁴, Nathalie Rouach¹⁵, Ivan Ruminot¹⁶, Aiman S Saab¹⁷, Carmen Sandi¹⁸, Stefanie Schirmeier¹⁹, Avital Schurr²⁰, Jimena Sierralta²¹, Maite Solas²², Vanja Tepavcevic²³, Bruno Weber¹⁷, Eduardo R Zimmer²⁴

Affiliations

¹ Institute of Functional Biology and Genomics, University of Salamanca, CSIC and Institute of Biomedical Research of Salamanca, Salamanca, Spain.
² Center for Neural Science, New York University, New York, New York, USA.
³ Centro de Estudios Científicos and Facultad de Medicina, Universidad San Sebastián, Valdivia, Chile.
⁴ Université Paris-Saclay, CNRS, Institut des Neurosciences Paris-Saclay, Saclay, France.
⁵ Universiy of Bordeaux, CNRS, CRMSB, UMR 5536, Bordeaux, France.
⁶ Center for Biomolecular Interactions Bremen and Center for Environmental Research and Sustainable Technologies, University of Bremen, Bremen, Germany.
⁷ Centre for Discovery Brain Sciences, Simons Initiative for the Developing Brain and Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
⁸ Carl-Ludwig-Institute for Physiology, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
⁹ Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
¹⁰ Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
¹¹ University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
¹² Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
¹³ RMETIST, U1313, University of Poitiers and CHU of Poitiers, Poitiers, France.
¹⁴ Energy and Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France.
¹⁵ Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, Inserm, Université PSL, PSL-NEURO, Paris, France.
¹⁶ Centro de Estudios Científicos-CECs and Facultad de Ciencias Para el Cuidado de la Salud, Universidad San Sebastián, Valdivia, Chile.
¹⁷ Institute of Pharmacology and Toxicology and Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.
¹⁸ Laboratory of Behavioral Genetics, Brain Mind Institute, and Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
¹⁹ Department of Biology, Technische Universität Dresden, Dresden, Germany.
²⁰ Department of Anesthesiology and Perioperative Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA.
²¹ Biomedical Neuroscience Institute and Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Independencia, Chile.
²² Department of Pharmaceutical Sciences, Division of Pharmacology, University of Navarra and IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
²³ Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain.
²⁴ Department of Pharmacology, Institute of Health Basic Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

PMID: 40686252
DOI: 10.1111/jnc.70166

Editorial

Embracing the Modern Biochemistry of Brain Metabolism

Juan P Bolaños et al. J Neurochem. 2025 Jul.

. 2025 Jul;169(7):e70166.

doi: 10.1111/jnc.70166.

Authors

Affiliations

¹ Institute of Functional Biology and Genomics, University of Salamanca, CSIC and Institute of Biomedical Research of Salamanca, Salamanca, Spain.
² Center for Neural Science, New York University, New York, New York, USA.
³ Centro de Estudios Científicos and Facultad de Medicina, Universidad San Sebastián, Valdivia, Chile.
⁴ Université Paris-Saclay, CNRS, Institut des Neurosciences Paris-Saclay, Saclay, France.
⁵ Universiy of Bordeaux, CNRS, CRMSB, UMR 5536, Bordeaux, France.
⁶ Center for Biomolecular Interactions Bremen and Center for Environmental Research and Sustainable Technologies, University of Bremen, Bremen, Germany.
⁷ Centre for Discovery Brain Sciences, Simons Initiative for the Developing Brain and Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
⁸ Carl-Ludwig-Institute for Physiology, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
⁹ Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
¹⁰ Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
¹¹ University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
¹² Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
¹³ RMETIST, U1313, University of Poitiers and CHU of Poitiers, Poitiers, France.
¹⁴ Energy and Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France.
¹⁵ Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, Inserm, Université PSL, PSL-NEURO, Paris, France.
¹⁶ Centro de Estudios Científicos-CECs and Facultad de Ciencias Para el Cuidado de la Salud, Universidad San Sebastián, Valdivia, Chile.
¹⁷ Institute of Pharmacology and Toxicology and Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.
¹⁸ Laboratory of Behavioral Genetics, Brain Mind Institute, and Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
¹⁹ Department of Biology, Technische Universität Dresden, Dresden, Germany.
²⁰ Department of Anesthesiology and Perioperative Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA.
²¹ Biomedical Neuroscience Institute and Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Independencia, Chile.
²² Department of Pharmaceutical Sciences, Division of Pharmacology, University of Navarra and IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
²³ Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain.
²⁴ Department of Pharmacology, Institute of Health Basic Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

PMID: 40686252
DOI: 10.1111/jnc.70166

Abstract

This editorial challenges the long-held neuron-centered view of brain metabolism, relying on ample evidence that it is a cooperative, multicellular process. Astrocytes, oligodendrocytes, and other glia play active roles providing lactate, antioxidant support, and substrate shuttles that fuel neuronal function and memory. Despite mounting data, some critics persist in refuting intercellular metabolic exchange, often guided more by entrenched creeds than concrete evidence, slowing constructive, hypothesis-driven discourse and delaying clinical and neuroprotective advances. The authors call for a rigorous research agenda: cell-type-specific manipulations, advanced biosensors, imaging and biomarkers, and integration with behavior and electrophysiology. They urge redirecting focus from outdated dogma to physiology-driven exploration of glia-neuron metabolic partnerships.

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References

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1. Ardanaz, C. G., A. de la Cruz, P. S. Minhas, et al. 2024. “Astrocytic GLUT1 Reduction Paradoxically Improves Central and Peripheral Glucose Homeostasis.” Science Advances 10: eadp1115.
1. Asadollahi, E., A. Trevisiol, A. S. Saab, et al. 2024. “Oligodendroglial Fatty Acid Metabolism as a Central Nervous System Energy Reserve.” Nature Neuroscience 27: 1934–1944.
1. Banerjee, A., S. Ghatak, and S. K. Sikdar. 2016. “L‐Lactate Mediates Neuroprotection Against Ischaemia by Increasing TREK1 Channel Expression in Rat Hippocampal Astrocytes In Vitro.” Journal of Neurochemistry 138: 265–281.
1. Belanger, M., J. Yang, J. M. Petit, T. Laroche, P. J. Magistretti, and I. Allaman. 2011. “Role of the Glyoxalase System in Astrocyte‐Mediated Neuroprotection.” Journal of Neuroscience 31: 18338–18352.

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Embracing the Modern Biochemistry of Brain Metabolism

Affiliations

Embracing the Modern Biochemistry of Brain Metabolism

Authors

Affiliations

Abstract

References

Publication types

MeSH terms