Depletion and activation of microglia impact metabolic connectivity of the mouse brain.


Journal

Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974

Informations de publication

Date de publication:
24 Feb 2023
Historique:
received: 03 07 2022
accepted: 13 02 2023
entrez: 24 2 2023
pubmed: 25 2 2023
medline: 3 3 2023
Statut: epublish

Résumé

We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG-PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated. We analyzed metabolic networks measured by interregional correlation coefficients (ICCs) 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 ( Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6-7 m; p = 0.0148, 9-10 m; p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn 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.

Identifiants

pubmed: 36829182
doi: 10.1186/s12974-023-02735-8
pii: 10.1186/s12974-023-02735-8
pmc: PMC9951492
doi:

Substances chimiques

Fluorodeoxyglucose F18 0Z5B2CJX4D
Progranulins 0
Trem2 protein, mouse 0
Membrane Glycoproteins 0
Receptors, Immunologic 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

47

Subventions

Organisme : Alzheimer Forschung Initiative e.V.
ID : 18014
Organisme : Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy
ID : 390857198
Organisme : Koselleck Project
ID : HA1737/16-1

Informations de copyright

© 2023. The Author(s).

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Auteurs

Johannes Gnörich (J)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

Anika Reifschneider (A)

Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.

Karin Wind (K)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

Artem Zatcepin (A)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

Sebastian T Kunte (ST)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Philipp Beumers (P)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Laura M Bartos (LM)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Thomas Wiedemann (T)

Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.

Maximilian Grosch (M)

German Center for Vertigo and Balance Disorders, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Xianyuan Xiang (X)

Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.
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-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.

Maryam K Fard (MK)

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

Francois Ruch (F)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Georg Werner (G)

Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.

Mara Koehler (M)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Luna Slemann (L)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Selina Hummel (S)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Nils Briel (N)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.

Tanja Blume (T)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.

Yuan Shi (Y)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.

Gloria Biechele (G)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Leonie Beyer (L)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Florian Eckenweber (F)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Maximilian Scheifele (M)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Peter Bartenstein (P)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Nathalie L Albert (NL)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.

Jochen Herms (J)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Sabina Tahirovic (S)

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

Christian Haass (C)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Anja Capell (A)

Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.

Sibylle Ziegler (S)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Matthias Brendel (M)

Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany. Matthias.Brendel@med.uni-muenchen.de.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. Matthias.Brendel@med.uni-muenchen.de.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Matthias.Brendel@med.uni-muenchen.de.

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