Current technical approaches to brain energy metabolism

Neuroscience is a technology‐driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells. Energy metabolism is not just a necessity for proper cell function and viability but plays specific roles in higher brain functions such as memory processing and behavior, whose mechanisms need to be understood at all hierarchical levels, from isolated proteins to whole subjects, in both health and disease. To this aim, the field takes advantage of diverse disciplines including anatomy, histology, physiology, biochemistry, bioenergetics, cellular biology, molecular biology, developmental biology, neurology, and mathematical modeling. This article presents a well‐referenced synopsis of the technical side of brain energy metabolism research. Detail and jargon are avoided whenever possible and emphasis is given to comparative strengths, limitations, and weaknesses, information that is often not available in regular articles.Fondecyt, Grant Number: 1160317; MINECO, Grant Numbers: SAF2016‐78114‐R and RTC‐2015‐3237‐1; CIBERFES, Grant Numer: CB16/10/00282; SP3‐People‐MC‐ITN program, Grant Number: 608381; EU BATCure, Grant Number: 666918; FEDER (European regional development fund); Investissement d'Avenir, Grant Number: ANR‐11‐INBS‐0011; French State in the context of the “Investments for the future” Program IdEx and the LabEx TRAIL, Grant Numbers: ANR‐10‐IDEX and ANR‐10‐LABX‐57; French–Swiss ANR‐FNS, Grant Numer: ANR‐15‐ CE37‐0012. University of Nottingham; BBSRC, Grant Numers: BB/L019396/1 and BB/K009192/1; MRC, Grant Number: MR/L020661/1; Deutsche Forschungsgemeinschaft, Grant Numers: DFG SPP 1757, SFB 894, and FOR 2289; European Commission, Grant Number: H2020‐FETPROACT 732344; Neurofibres, Grant Number: H2020‐MSCA‐ITN‐722053 EU‐GliaPhD; US National Institutes of Health, Grant Number: R01NS087611; Teva Pharmaceuticals; Agilent Technologies. IdEx, Grant Number: ANR‐10‐IDEX‐03‐02; French–Swiss ANR‐FNS, Grant number: 310030E‐164271; National Institutes of Neurologic Disease and Stroke at the National Institutes of Health, Grant Numer: R01 NS077773; University of Zurich and the Swiss National Science Foundation; Comisión Nacional de Investigación Científica y Tecnológica, Grant Numer: PB 01; Fondo Nacional de Desarrollo Científico y Tecnológico, Grant Numer: 1160317; Ministerio de Economía y Competitividad, Grant Numer: RTC‐2015‐3237‐1,SAF2016‐78114‐R; Agence Nationale de la Recherche, Grant Numers: ANR‐10‐IDEX, ANR‐10‐IDEX‐03‐02, ANR‐10‐LABX‐57, ANR‐11‐INBS‐0011, and ANR‐15‐ CE37‐0012; Biotechnology and Biological Sciences Research Council, Grant Numers: BB/L019396/1 and BB/K009192/1; Medical Research Council, Grant Numer: MR/L020661/1.Peer reviewe