Astroglial glucose uptake determines brain FDG-PET alterations and metabolic connectivity during healthy aging in mice
Laura M. Bartos,
Sebastian T. Kunte,
Stephan Wagner,
Philipp Beumers,
Rebecca Schaefer,
Artem Zatcepin,
Yunlei Li,
Maria Griessl,
Leonie Hoermann,
Karin Wind-Mark,
Peter Bartenstein,
Sabina Tahirovic,
Sibylle Ziegler,
Matthias Brendel,
Johannes Gnörich
Affiliations
Laura M. Bartos
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Sebastian T. Kunte
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Stephan Wagner
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Philipp Beumers
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Rebecca Schaefer
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Artem Zatcepin
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany
Yunlei Li
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Maria Griessl
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Leonie Hoermann
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Karin Wind-Mark
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany
Peter Bartenstein
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Sabina Tahirovic
German Center for Neurodegenerative Diseases (DZNE) Munich, Germany
Sibylle Ziegler
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Matthias Brendel
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Johannes Gnörich
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany; Corresponding author at: Marchinonistrasse 15, 81377 Munich, Germany
Purpose: 2-Fluorodeoxyglucose-PET (FDG-PET) is a powerful tool to study glucose metabolism in mammalian brains, but cellular sources of glucose uptake and metabolic connectivity during aging are not yet understood. Methods: Healthy wild-type mice of both sexes (2–21 months of age) received FDG-PET and cell sorting after in vivo tracer injection (scRadiotracing). FDG uptake per cell was quantified in isolated microglia, astrocytes and neurons. Cerebral FDG uptake and metabolic connectivity were determined by PET. A subset of mice received measurement of blood glucose levels to study associations with cellular FDG uptake during aging. Results: Cerebral FDG-PET signals in healthy mice increased linearly with age. Cellular FDG uptake of neurons increased between 2 and 12 months of age, followed by a strong decrease towards late ages. Contrarily, FDG uptake in microglia and astrocytes exhibited a U-shaped function with respect to age, comprising the predominant cellular source of higher cerebral FDG uptake in the later stages. Metabolic connectivity was closely associated with the ratio of glucose uptake in astroglial cells relative to neurons. Cellular FDG uptake was not associated with blood glucose levels and increasing FDG brain uptake as a function of age was still observed after adjusting for blood glucose levels. Conclusion: Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.
