Brain energy metabolism: A roadmap for future research

Author:

Rae Caroline D.1ORCID,Baur Joseph A.2,Borges Karin3ORCID,Dienel Gerald45,Díaz‐García Carlos Manlio6ORCID,Douglass Starlette R.7ORCID,Drew Kelly8,Duarte João M. N.9ORCID,Duran Jordi1011,Kann Oliver12ORCID,Kristian Tibor1314,Lee‐Liu Dasfne15ORCID,Lindquist Britta E.16ORCID,McNay Ewan C.7ORCID,Robinson Michael B.17ORCID,Rothman Douglas L.18ORCID,Rowlands Benjamin D.19ORCID,Ryan Timothy A.20,Scafidi Joseph21,Scafidi Susanna22ORCID,Shuttleworth C. William23ORCID,Swanson Raymond A.24ORCID,Uruk Gökhan24,Vardjan Nina2526,Zorec Robert2526,McKenna Mary C.27ORCID

Affiliation:

1. School of Psychology The University of New South Wales, NSW 2052 & Neuroscience Research Australia Randwick New South Wales Australia

2. Department of Physiology and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

3. School of Biomedical Sciences, Faculty of Medicine The University of Queensland St Lucia QLD Australia

4. Department of Neurology University of Arkansas for Medical Sciences Little Rock Arkansas USA

5. Department of Cell Biology and Physiology University of New Mexico School of Medicine Albuquerque New Mexico USA

6. Department of Biochemistry and Molecular Biology, Center for Geroscience and Healthy Brain Aging University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA

7. Behavioral Neuroscience University at Albany Albany New York USA

8. Center for Transformative Research in Metabolism, Institute of Arctic Biology University of Alaska Fairbanks Fairbanks Alaska USA

9. Department of Experimental Medical Science, Faculty of Medicine Lund University, Lund, & Wallenberg Centre for Molecular Medicine, Lund University Lund Sweden

10. Institut Químic de Sarrià (IQS) Universitat Ramon Llull (URL) Barcelona Spain

11. Institute for Bioengineering of Catalonia (IBEC) The Barcelona Institute of Science and Technology Barcelona Spain

12. Institute of Physiology and Pathophysiology University of Heidelberg, D‐69120; Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg Heidelberg Germany

13. Veterans Affairs Maryland Health Center System Baltimore Maryland USA

14. Department of Anesthesiology and the Center for Shock, Trauma, and Anesthesiology Research (S.T.A.R.) University of Maryland School of Medicine Baltimore Maryland USA

15. Facultad de Medicina y Ciencia Universidad San Sebastián Santiago Región Metropolitana Chile

16. Department of Neurology, Division of Neurocritical Care, Gladstone Institute of Neurological Disease University of California at San Francisco San Francisco California USA

17. Departments of Pediatrics and System Pharmacology & Translational Therapeutics, Children's Hospital of Philadelphia University of Pennsylvania Philadelphia Pennsylvania USA

18. Magnetic Resonance Research Center and Departments of Radiology and Biomedical Engineering Yale University New Haven Connecticut USA

19. School of Chemistry, Faculty of Science The University of Sydney Sydney New South Wales Australia

20. Department of Biochemistry Weill Cornell Medicine New York New York USA

21. Department of Neurology, Kennedy Krieger Institute Johns Hopkins University School of Medicine Baltimore Maryland USA

22. Anesthesiology & Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USA

23. Department of Neurosciences University of New Mexico School of Medicine Albuquerque Albuquerque New Mexico USA

24. Department of Neurology University of California, San Francisco, and San Francisco Veterans Affairs Medical Center San Francisco California USA

25. Laboratory of Cell Engineering Celica Biomedical Ljubljana Slovenia

26. Laboratory of Neuroendocrinology—Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine University of Ljubljana Ljubljana Slovenia

27. Department of Pediatrics and Program in Neuroscience University of Maryland School of Medicine Baltimore Maryland USA

Abstract

AbstractAlthough we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research.

Funder

International Society for Neurochemistry

Publisher

Wiley

Subject

Cellular and Molecular Neuroscience,Biochemistry

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