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Neuron
Published

Microglia protect against age-associated brain pathologies

Authors

David A D Munro, Nadine Bestard-Cuche, Conor McQuaid, Audrey Chagnot, Sepideh Kiani Shabestari, Jean Paul Chadarevian, Upasana Maheshwari, Stefan Szymkowiak, Kim Morris, Mehreen Mohammad, Andrea Corsinotti, Barry Bradford, Neil Mabbott, Ross J Lennen, Maurits A Jansen, Clare Pridans, Barry W McColl, Annika Keller, Mathew Blurton-Jones, Axel Montagne, Anna Williams, Josef Priller

Abstract

Neuron. 2024 Jun 17:S0896-6273(24)00365-9. doi: 10.1016/j.neuron.2024.05.018. Online ahead of print.

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.

PMID:38897208 | DOI:10.1016/j.neuron.2024.05.018

UK DRI Authors

Axel Montagne

Dr Axel Montagne

Group Leader

Exploring the link between cerebrovascular and inflamm-ageing to neurodegeneration and dementia

Dr Axel Montagne