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