Journal Article

DZNE-2024-01066

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Microglia protect against age-associated brain pathologies.

Munro, D. A. D. ; Bestard-Cuche, N. ; McQuaid, C. ; Chagnot, A. ; Shabestari, S. K. ; Chadarevian, J. P. ; Maheshwari, U. ; Szymkowiak, S. ; Morris, K. ; Mohammad, M. ; Corsinotti, A. ; Bradford, B. ; Mabbott, N. ; Lennen, R. J. ; Jansen, M. A. ; Pridans, C. ; McColl, B. W. ; Keller, A. ; Blurton-Jones, M. ; Montagne, A. ; Williams, A. ; Priller, J. (Last author)DZNE*

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2024.05.018

Abstract: Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the Csf1rΔFIRE/ΔFIRE mouse model. In juvenile Csf1rΔFIRE/ΔFIRE mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types. By contrast, with advancing age, pathologies accumulate in Csf1rΔFIRE/ΔFIRE brains, macroglia become increasingly dysregulated, and white matter integrity declines, mimicking many pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly vulnerable to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular alterations, macroglial dysregulation, and severe tissue calcification. We show that populating Csf1rΔFIRE/ΔFIRE brains with wild-type microglia protects against many of these pathological changes. Together with the accompanying study by Chadarevian and colleagues1, our results indicate that the lifelong absence of microglia results in an age-related neurodegenerative condition that can be counteracted via transplantation of healthy microglia.

Keyword(s): Microglia: pathology (MeSH) ; Microglia: metabolism (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Aging: pathology (MeSH) ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: metabolism (MeSH) ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: genetics (MeSH) ; Brain: pathology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Male (MeSH) ; White Matter: pathology (MeSH) ; Leukoencephalopathies: pathology (MeSH) ; Thalamus: pathology (MeSH) ; aging ; brain calcification ; macroglia ; microglia ; neurodegeneration ; transplantation ; Csf1r protein, mouse ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

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Contributing Institute(s):

1. Translational Neuropsychiatry (AG Priller)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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