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Götzl, J.K.* ; Brendel, M.* ; Werner, G.* ; Parhizkar, S.* ; Sebastian Monasor, L.* ; Kleinberger, G.* ; Colombo, A.V.* ; Deussing, M.* ; Wagner, M. ; Winkelmann, J. ; Diehl-Schmid, J.* ; Levin, J.* ; Fellerer, K.* ; Reifschneider, A.* ; Bultmann, S.* ; Bartenstein, P.* ; Rominger, A.* ; Tahirovic, S.* ; Smith, S.T.* ; Madore, C.* ; Butovsky, O.* ; Capell, A.* ; Haass, C.*

Opposite microglial activation stages upon loss of PGRN or TREM2 result in reduced cerebral glucose metabolism.

EMBO Mol. Med. 11, e9711 (2019)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Microglia adopt numerous fates with homeostatic microglia (HM) and a microglial neurodegenerative phenotype (MGnD) representing two opposite ends. A number of variants in genes selectively expressed in microglia are associated with an increased risk for neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Among these genes are progranulin (GRN) and the triggering receptor expressed on myeloid cells 2 (TREM2). Both cause neurodegeneration by mechanisms involving loss of function. We have now isolated microglia from Grn−/− mice and compared their transcriptomes to those of Trem2−/− mice. Surprisingly, while loss of Trem2 enhances the expression of genes associated with a homeostatic state, microglia derived from Grn−/− mice showed a reciprocal activation of the MGnD molecular signature and suppression of gene characteristic for HM. The opposite mRNA expression profiles are associated with divergent functional phenotypes. Although loss of TREM2 and progranulin resulted in opposite activation states and functional phenotypes of microglia, FDG (fluoro-2-deoxy-d-glucose)-μPET of brain revealed reduced glucose metabolism in both conditions, suggesting that opposite microglial phenotypes result in similar wide spread brain dysfunction.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Disease-associated And Homeostatic Microglial Signatures ; Microglia ; Neurodegeneration ; Progranulin ; Trem2
ISSN (print) / ISBN 1757-4676
e-ISSN 1757-4684
Journal EMBO Molecular Medicine
Quellenangaben Volume: 11, Issue: 5, Pages: e9711 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Chichester
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Neurogenomics (ING)