Nuklearmedizin 2023; 62(02): 89-90
DOI: 10.1055/s-0043-1766159
Abstracts | NuklearMedizin 2023
Leuchtturm
Neurologie

Depletion and activation of microglia alter metabolic connectivity of the mouse brain

Authors

  • J. Gnörich

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • A. Reifschneider

    2   Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, LMU Munich, Germany, Munich

  • K. Wind

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • A. Zatcepin

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • S. Kunte

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • P. Beumers

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • L. Bartos

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • T. Wiedemann

    2   Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, LMU Munich, Germany, Munich

  • M. Grosch

    3   German Center for Vertigo and Balance Disorders, University Hospital, LMU Munich, Munich, Germany, Munich

  • X. Xiang

    4   CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen

  • M. Khojasteh-Fard

    5   German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany, Munich

  • F. Ruch

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • G. Werner

    2   Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, LMU Munich, Germany, Munich

  • M. Koehler

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • L. Slemann

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • S. Hummel

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • C. Haass

    5   German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany, Munich

  • A. Capell

    2   Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, LMU Munich, Germany, Munich

  • S. Ziegler

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich

  • M. Brendel

    1   Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich
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Ziel/Aim We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity since microglial activation states determine FDG-PET alterations.

Methodik/Methods We analyzed metabolic networks measured by interregional correlation coefficients of FDG-PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts (-/-) as well as in double mutant Grn-/- / Trem2-/- mice. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied. FDG uptake of neurons, microglia, and astrocytes was determined in Grn-/- and WT mice via assessment of single cell tracer uptake.

Ergebnisse/Results Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity in WT mice at both ages studied (6-7m; p=0.0148, 9-10m; p=0.0191), when compared to vehicle-treated age-matched WT mice. Grn-/-, Trem2-/- and Grn-/-/Trem2-/- mice all displayed reduced FDG-PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn-/-mice when compared to WT mice in cortical (p<0.0001) and hippocampal (p<0.0001) networks. In contrast, Trem2-/-mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn-/-mice was completely suppressed in Grn-/-/Trem2-/- mice. Grn-/-mice exhibited a severe loss of neuronal FDG uptake (–61%, p<0.0001) which shifted allocation of cellular brain FDG uptake to microglia (42% in Grn-/-vs. 22% in WT).

Schlussfolgerungen/Conclusions Presence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation.


Publication History

Article published online:
30 March 2023

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