title: Imaging the time-integrated cerebral metabolic activity with subcellular resolution through nanometer-scale detection of biosynthetic products deriving from (13)C-glucose.
abstract: Glucose is the primary source of energy for the brain but also an important source of building blocks for proteins, lipids, and nucleic acids. Little is known about the use of glucose for biosynthesis in tissues at the cellular level. We demonstrate that local cerebral metabolic activity can be mapped in mouse brain tissue by quantitatively imaging the biosynthetic products deriving from [U-(13)C]glucose metabolism using a combination of in situ electron microscopy and secondary ion mass-spectroscopy (NanoSIMS). Images of the (13)C-label incorporated into cerebral ultrastructure with ca. 100 nm resolution allowed us to determine the timescale on which the metabolic products of glucose are incorporated into different cells, their sub-compartments and organelles. These were mapped in astrocytes and neurons in the different layers of the motor cortex. We see evidence for high metabolic activity in neurons via the nucleus (13)C enrichment. We observe that in all the major cell compartments, such as e.g. nucleus and Golgi apparatus, neurons incorporate substantially higher concentrations of (13)C-label than astrocytes.
authors.affiliation: Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering (ENAC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: takado@nirs.go.jp.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Takado
authors.affiliation: Centre Interdisciplinaire de Microscopie Electronique, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Graham
authors.initials: G
authors.lastname: Knott
authors.affiliation: Electron Microscopy Facility, Université de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Humbel
authors.affiliation: Nestlé Institute of Health Science, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.affiliation: Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering (ENAC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Escrig
authors.affiliation: Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering (ENAC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Center for Advanced Surface Analysis, Institute of Earth Sciences, Université de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: anders.meibom@epfl.ch.
authors.forename: Anders
authors.initials: A
authors.lastname: Meibom
authors.affiliation: Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: arnaud.comment@epfl.ch.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Comment
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002247:Carbon Isotopes; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron / Q000379:methods; D057054:Molecular Imaging / Q000379:methods; D009044:Motor Cortex / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism*; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods
chemical_list: D002247:Carbon Isotopes; D005947:Glucose
keywords: Astrocytes; Glucose; Microscopy; Molecular imaging; Neuronal–glial interaction