Journal Article

DZNE-2024-01186

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Astroglial glucose uptake determines brain FDG-PET alterations and metabolic connectivity during healthy aging in mice

Bartos, L. M. ; Kunte, S. T. ; Wagner, S. ; Beumers, P. ; Schaefer, R. ; Zatcepin, A.DZNE* ; Li, Y.Extern* ; Griessl, M. ; Hoermann, L. ; Wind-Mark, K.DZNE* ; Bartenstein, P. ; Tahirovic, S.DZNE* ; Ziegler, S. ; Brendel, M.DZNE* ; Gnörich, J. (Last author)DZNE*

2024
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.neuroimage.2024.120860

Abstract: 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.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.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.Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.

Keyword(s): Animals (MeSH) ; Fluorodeoxyglucose F18: pharmacokinetics (MeSH) ; Astrocytes: metabolism (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Mice (MeSH) ; Glucose: metabolism (MeSH) ; Male (MeSH) ; Brain: metabolism (MeSH) ; Brain: diagnostic imaging (MeSH) ; Female (MeSH) ; Mice, Inbred C57BL (MeSH) ; Aging: metabolism (MeSH) ; Radiopharmaceuticals: pharmacokinetics (MeSH) ; Neurons: metabolism (MeSH) ; Healthy Aging: metabolism (MeSH) ; Microglia: metabolism (MeSH) ; Aging ; Astroglia ; FDG-PET ; Metabolic connectivity ; Scradiotracing ; Fluorodeoxyglucose F18 ; Glucose ; Radiopharmaceuticals

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Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)
2. Juvenile Neurodegeneration (AG Tahirovic)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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