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@ARTICLE{Kunte:281534,
      author       = {Kunte, Sebastian T and Gnoerich, Johannes and Beumers,
                      Philipp and Bartos, Laura M and Wagner, Stephan and Wind,
                      Karin and Holzgreve, Adrien and Pötter, Dennis and Werner,
                      Rudolf A and Ziegler, Sibylle and Albert, Nathalie L and
                      Colombo, Alessio and Tahirovic, Sabina and Brendel,
                      Matthias},
      title        = {{D}istinct reduction in relative microglial glucose uptake
                      compared to astrocytes and neurons upon isolation from the
                      brain environment.},
      journal      = {Frontiers in cellular neuroscience},
      volume       = {19},
      issn         = {1662-5102},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {DZNE-2025-01152},
      pages        = {1572431},
      year         = {2025},
      abstract     = {Microglial energy metabolism has gained attention for the
                      treatment of neurodegenerative diseases. In vitro methods
                      provide important insights; however, it remains unclear
                      whether the metabolism of highly motile microglia is
                      preserved outside their regular environment. Therefore, we
                      directly compared the microglial glucose uptake in vivo and
                      in vitro in mice.Microglia and astrocytes were isolated from
                      the brain using immunomagnetic cell sorting following
                      [18F]FDG injection in living mice, followed by gamma and
                      single-cell radiotracing (scRadiotracing). Enriched cell
                      fractions were incubated with excess [18F]FDG (50,000-fold)
                      in vivo, washed, and measured equivalently. For all
                      fractions, radioactivity per cell was normalized to the
                      injected or incubated radioactivity, and ratios of
                      microglialuptake were calculated relative to astrocytes and
                      the microglia/astrocyte-negative fraction. The experiment
                      was repeated using a glucose-free buffer and validated by in
                      vitro incubation without prior in vivo [18F]FDG injection to
                      exclude the influence of fasting and glucose
                      injection.scRadiotracing results were compared against cell
                      culture [18F]-FDG incubation. The in vivo glucose uptake of
                      microglia was higher when compared to astrocytes (50.4-fold,
                      p < 0.0001) and non-microglia/ non-astrocyte cells
                      (10.6-fold, p < 0.0001). Microglia still exhibited the
                      highest glucose uptake in vitro, but with a distinct
                      reduction in microglia-to-astrocyte (5.7-fold, p < 0.0015)
                      and microglia-to-microglia/astrocyte-negative ratios (1.7
                      fold, p < 0.0001). Fasting and in vitro incubation were used
                      to validate the results. Cell culture indicated low
                      microglial uptake compared to that in neurons (1:100) or
                      astrocytes (1:10).Compared to astrocytes and other cells,
                      microglia show a distinct reduction in uptake in vitro
                      compared to in vivo uptake. Our results emphasize that in
                      vitro experiments should be interpreted with caution when
                      studying microglial energy metabolism.},
      keywords     = {glucose uptake (Other) / in vitro (Other) / in vivo (Other)
                      / microglia (Other) / scRadiotracing (Other)},
      cin          = {AG Haass / AG Tahirovic},
      ddc          = {610},
      cid          = {I:(DE-2719)1110007 / I:(DE-2719)1140003},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41030616},
      pmc          = {pmc:PMC12477191},
      doi          = {10.3389/fncel.2025.1572431},
      url          = {https://pub.dzne.de/record/281534},
}