title: Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism.
abstract: Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Iben
authors.initials: I
authors.lastname: Lundgaard
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Department of Clinical Pharmacology, China Medical University, 110001 Shenyang, China.
authors.forename: Baoman
authors.initials: B
authors.lastname: Li
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Lulu
authors.initials: L
authors.lastname: Xie
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Kang
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Sanggaard
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: John D R
authors.initials: JD
authors.lastname: Haswell
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Siri
authors.initials: S
authors.lastname: Goldman
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Solomiya
authors.initials: S
authors.lastname: Blekot
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Nielsen
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.affiliation: 1] Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA [2] Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose; D059907:Functional Neuroimaging / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007150:Immunohistochemistry; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019265:Spectroscopy, Near-Infrared; D014851:Wakefulness; D014991:Xylazine / Q000494:pharmacology
chemical_list: D000778:Anesthetics, Dissociative; D000963:Antimetabolites; D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; D014991:Xylazine; D007649:Ketamine; D003847:Deoxyglucose; D006593:Hexokinase; D005947:Glucose