ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Microglia modulate hippocampal neural precursor activity in response to exercise and aging.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 232 citations in OpenAlex.
- Differential effects of environmental enrichment and physical exercise on glial biology in aging and aging-related conditions: a systematic review.Frontiers in cellular neuroscience · 2026Pooled it
- Long-Term Improvement in Hippocampal-Dependent Learning Ability in Healthy, Aged Individuals Following High Intensity Interval Training.Aging and disease · 2024Trial
- Restoration of gamma-aminobutyric acid homeostasis: A novel approach to alleviating central nervous system injury-associated immunodepression syndrome.Neural regeneration research · 2026Article
- Voluntary Exercise and Hippocampal Memory Enhancement: Decoding the Molecular Blueprint.Journal of molecular neuroscience : MN · 2026Review
- Review
- Morphological changes in microglia in the mouse brain during postnatal development and obesity.Histology and histopathology · 2026Article
- Neurogenesis and Neuroinflammation in Dialogue: Mapping Gaps, Modulating Microglia, Rewiring Aging.Cells · 2026Review
- The hippocampal subgranular zone neurogenic niche: a modular perspective on neural stem cell regulation.Frontiers in cellular neuroscience · 2026Review
- Exercise training promotes neurogenesis in the adult hippocampus with a particular focus on cell cycle regulation.Frontiers in sports and active living · 2026Review
- Plasma proteomics reveals molecular overlap between physical activity and dementia risk.Brain communications · 2026Article
- Advances in the multifunctional roles of CX3CL1 in the central nervous system.Frontiers in aging neuroscience · 2026Review
- Adult hippocampal neurogenesis: New avenues for treatment of brain disorders.Stem cell reports · 2025Review
- Gut microbiota regulates exercise-induced hormetic modulation of cognitive function.EBioMedicine · 2025Article
- Article
- Exercise, Diet, and Brain Health: From the Perspective of Gut Microbiota Regulation.Nutrients · 2025Review
- Muscle-driven spinal cord histological and transcriptomic alterations in a myotonic dystrophy mouse model: insights into neuropathy.Brain communications · 2025Article
- Controversies and insights into cytokine regulation of neurogenesis and behavior in adult rodents.Frontiers in immunology · 2025Review
- Hippocampal Neurogenesis via Light-Intensity Running and Its Mechanism.Advances in neurobiology · 2025Review
- Sex differences in the outcomes of modifiable lifestyle factors for cognitive aging: neuroinflammation and microglia as key underlying mechanisms.Frontiers in aging neuroscience · 2025Review
- Physical Exercise Benefits Cognition: A Narrative Review of Evidence and Possible Mechanisms.Advances in neurobiology · 2025Review
76 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
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may have the ability to differentially instruct neurogenesis in the adult brain. Here, we used transgenic Csf1r-GFP mice to investigate whether hippocampal microglia directly influence the activation of neural precursor cells. Our results revealed that an exercise-induced increase in neural precursor cell activity was mediated via endogenous microglia and abolished when these cells were selectively removed from hippocampal cultures. Conversely, microglia from the hippocampi of animals that had exercised were able to activate latent neural precursor cells when added to neurosphere preparations from sedentary mice. We also investigated the role of CX(3)CL1, a chemokine that is known to provide a more neuroprotective microglial phenotype. Intraparenchymal infusion of a blocking antibody against the CX(3)CL1 receptor, CX(3)CR1, but not control IgG, dramatically reduced the neurosphere formation frequency in mice that had exercised. While an increase in soluble CX(3)CL1 was observed following running, reduced levels of this chemokine were found in the aged brain. Lower levels of CX(3)CL1 with advancing age correlated with the natural decline in neural precursor cell activity, a state that could be partially alleviated through removal of microglia. These findings provide the first direct evidence that endogenous microglia can exert a dual and opposing influence on neural precursor cell activity within the hippocampus, and that signaling through the CX(3)CL1-CX(3)CR1 axis critically contributes toward this process.
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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.