ArticleAging cell2018
Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
200 citing papers in PubMed, 1 synthesis or guideline pooled it, 385 citations in OpenAlex.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Sex differences in the effects of chronic stress and oxycodone associative learning on glial markers in rat hippocampus.Neuroscience · 2026Article
- CSF1R+ macrophage and osteoclast depletion impairs neural crest proliferation and craniofacial morphogenesis.Development (Cambridge, England) · 2026Article
- CSF1R+ Macrophages and Osteoclasts Are Essential for Limb Bone Development During Embryogenesis.Journal of developmental biology · 2026Article
- Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy.Science (New York, N.Y.) · 2026Article
- Role of eCIRP in Mediating Post-ischemia Microglial Phagocytosis via TREM-2 Receptor: Insights from Porcine and Mouse Cellular Models.Molecular neurobiology · 2026Article
- Kupffer cells control neonatal hepatic metabolism via Igf1 signaling.Development (Cambridge, England) · 2026Article
- Neurogenesis and Neuroinflammation in Dialogue: Mapping Gaps, Modulating Microglia, Rewiring Aging.Cells · 2026Review
- Microglial activity during postnatal development is required for infantile amnesia in mice.PLoS biology · 2026Article
- Targeting microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and therapeutic approaches.Frontiers in immunology · 2026Review
- Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.Frontiers in neuroscience · 2026Review
- Coordinated cellular architecture reveals weakened cortical structure-behavior coupling in normal aging.Frontiers in aging neuroscience · 2026Article
- Editorial: The stem cell niche in brain aging and neurodegenerative disorders.Frontiers in aging neuroscience · 2026Article
- TREM2 as a central hub of neuroimmune-metabolic crosstalk in central nervous system disorders: from microglial biology to therapeutic targeting.Frontiers in immunology · 2026Review
- Dysfunction of lipid metabolism and lysosomal capacity: at the core of microglial aging?Frontiers in aging neuroscience · 2026Review
- Timed microglia depletion promotes functional network reorganization and motor recovery after stroke.Brain communications · 2026Article
- Cerebrolysin Ameliorates Age-Induced Dendritic Spine Degeneration and Memory Decline in C57BL6 Mice.Neurochemical research · 2025Article
- Inhibition of histone lysine demethylase restores learning and memory in aged mice.bioRxiv : the preprint server for biology · 2025Article
- Influenza A infection accelerates disease-associated microglia formation during physiological aging.bioRxiv : the preprint server for biology · 2025Article
140 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Microglia, the resident immune cell of the brain, can be eliminated via pharmacological inhibition of the colony-stimulating factor 1 receptor (CSF1R). Withdrawal of CSF1R inhibition then stimulates microglial repopulation, effectively replacing the microglial compartment. In the aged brain, microglia take on a "primed" phenotype and studies indicate that this coincides with age-related cognitive decline. Here, we investigated the effects of replacing the aged microglial compartment with new microglia using CSF1R inhibitor-induced microglial repopulation. With 28 days of repopulation, replacement of resident microglia in aged mice (24 months) improved spatial memory and restored physical microglial tissue characteristics (cell densities and morphologies) to those found in young adult animals (4 months). However, inflammation-related gene expression was not broadly altered with repopulation nor the response to immune challenges. Instead, microglial repopulation resulted in a reversal of age-related changes in neuronal gene expression, including expression of genes associated with actin cytoskeleton remodeling and synaptogenesis. Age-related changes in hippocampal neuronal complexity were reversed with both microglial elimination and repopulation, while microglial elimination increased both neurogenesis and dendritic spine densities. These changes were accompanied by a full rescue of age-induced deficits in long-term potentiation with microglial repopulation. Thus, several key aspects of the aged brain can be reversed by acute noninvasive replacement of microglia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.