Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.

Charles Perkins Centre School of Medical Sciences The University of Sydney Camperdown New South Wales Australia

Deparment of Molecular and Cellular Biochemistry College of Medicine University of Kentuchy Lexington Kentuchy USA

Departamento de Toxicología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Ciudad de México México

Department of Anatomy and Neurobiology Virginia Commonwealth University School of Medicine Richmond Virginia USA

Department of Biological Sciences University of Limerick Limerick Ireland

Department of Biology Technische Universität Dresden Dresden Germany

Department of Cell Biology and Physiology CSIR Indian Institute of Chemical Biology Kolkata India

Department of Drug Design and Pharmacology University of Copenhagen Copenhagen Denmark

Department of Immunology Instituto de Ciências Biomédicas Universidade de São Paulo São Paulo SP Brazil

Department of Neurology and Neurosurgery McGill University Montreal Quebec Canada

Department of Neurology Columbia University Irving Medical Centre New York New York USA

Department of Neurology Johns Hopkins University Baltimore Maryland USA

Division of Medical Sciences University of Victoria Victoria British Columbia Canada

Florey Institute of Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia

Institute of Medical Biochemistry Leopoldo De Meis Federal University of Rio de Janeiro Rio de Janeiro Brazil

Laboratory for Translational Research in Neuropsychiatric Disorders BRAINCITY Center of Excellence for Neural Plasticity and Brain Disorders Institute of Experimental Biology Marceli Nencki Polish Academy of Sciences Warsaw Poland

Laboratory of Neurochemistry Institute of Physiology of the Czech Academy of Sciences Prague Czech Republic

Łukasiewicz Research Network PORT Polish Center for Technology Development Wroclaw Poland

School of Biomedical Sciences The University of Queensland St Lucia Queensland Australia

Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada

The Edmond and Lily Safra Center for Brain Sciences The Hebrew University of Jerusalem Jerusalem Israel

The Michael 5 Johnston Center for Developmental Neuroscience Kennedy Krieger Institute Baltimore Maryland USA

Univ Bordeaux INRAE Bordeaux INP NutriNeurO Bordeaux France

Univ Bordeaux INSERM Neurocentre Magendie U1215 F 33000 Bordeaux France

Univ Lyon Université Claude Bernard Lyon 1 CNRS INSERM Physiopathologie et Génétique du Neurone et du Muscle UMR5261 U1315 Institut NeuroMyoGène Lyon France

Università Degli Studi di Milano Milan Italy

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