Thursday, June 20, 2024

Microglia protect against age-associated brain pathologies

 If you  have a competent? doctor they will get human testing going and create interventions that save these microglia! Do you have a competent doctor?

Microglia protect against age-associated brain pathologies

Open AccessPublished:June 18, 2024DOI:https://doi.org/10.1016/j.neuron.2024.05.01

Highlights

  • Lack of microglia leads to progressive brain calcifications and macroglial reactivity
  • scRNA-seq reveals brain cell profiles across the lifespan in the absence of microglia
  • The thalamus is particularly sensitive to the absence of microglia with aging
  • Transplanting microglia protects against pathology development

Summary

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 colleagues, 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.

Graphical abstract


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