Microglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging
Open accessAbstract
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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Microglia depletion in hippocampal culture from aged mice, but not from young mice, promoted formation of neurospheres, suggesting an anti-neurogenic role of microglia in the aged brain.
“For instance, microglia depletion in hippocampal culture from aged mice, but not from young mice, promoted formation of neurospheres (indicative of neural progenitor cell proliferation), suggesting an anti-neurogenic role of microglia in the aged brain (Vukovic et al, 2012).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Vukovic et al, 2012
The hippocampus is particularly susceptible to age-associated functional impairments and overt pathology such as neuronal degeneration.
“For example, the hippocampus is particularly susceptible to age-associated functional impairments and overt pathology such as neuronal degeneration (Mosher and Wyss-Coray, 2014;Vukovic et al, 2012;West et al, 1994).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Vukovic et al, 2012
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- Authors
- Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Bartlett, Perry F.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-05-09
- Volume
- 32
- Issue
- 19
- Pages
- 6435-6443
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6621117
- OpenAlex
- W2089621097
- Cited by
- 241
- References
- 55
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 16 · 2023: 7 · 2022: 16 · 2021: 18 · 2020: 22 · 2019: 17 · 2018: 12 · 2017: 18 · 2016: 15 · 2015: 18 · 2014: 24 · 2013: 21 · 2012: 9
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Queensland
- Queensland Government
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, adult hippocampal neurogenesis, neural progenitor cells, physical activity, aging, fractalkine, CX3CR1, neurospheres, microglial depletion, running, chemokine signaling
- MeSH terms
- Aging, Animals, Female, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Physical Conditioning, Animal, Microglia, Mice, Knockout, Mice, Neurogenesis, Neural Stem Cells
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