Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice
Open accessAbstract
Aging is associated with low-grade neuroinflammation including primed microglia that may contribute to deficits in neural plasticity and cognitive function. The current study evaluated whether exercise modulates division and/or activation state of microglia in the dentate gyrus of the hippocampus, as activated microglia can express a classic inflammatory or an alternative neuroprotective phenotype. We also assessed hippocampal neurogenesis to determine whether changes in microglia were associated with new neuron survival. Adult (3.5 months) and aged (18 months) male BALB/c mice were individually housed with or without running wheels for 8 weeks. Mice received bromodeoxyuridine injections during the first or last 10 days of the experiment to label dividing cells. Immunofluorescence was conducted to measure microglia division, co-expression of the neuroprotective indicator insulin-like growth factor (IGF-1), and new neuron survival. The proportion of new microglia was increased in aged mice, and decreased from wheel running. Running increased the proportion of microglia expressing IGF-1 suggesting exercise shifts microglia phenotype towards neuroprotection. Additionally, running enhanced survival of new neurons in both age groups. Findings suggest that wheel running may attenuate microglia division and promote a proneurogenic phenotype in aged mice.
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Igf1 is abundantly expressed by microglia during postnatal development, aging, or following brain injuries and plays a vital role in promoting neuronal survival.
“Igf1 is abundantly expressed by microglia during postnatal development, aging or following brain injuries and plays a vital role in promoting neuronal survival (59,63–66).”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [65]
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“Igf1 is abundantly expressed by microglia during postnatal development, aging, or following brain injuries and plays a vital role in promoting neuronal survival (Fernandez and Torres-Aleman 2012; Kohman et al. 2012; Thored et al. 2009; Ueno et al. 2013).”
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“[84], demonstrating that running increased the proportion of microglia expressing IGF-1 and the survival of neurons, suggesting that exercise shifts toward microglia pro-neurogenic phenotype allowing neuroprotection.”
Background
- Authors
- Kohman, R. A., DeYoung, E. K., Bhattacharya, T. K., Peterson, L. N., & Rhodes, J. S.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Kohman, Rachel A.
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 26
- Issue
- 5
- Pages
- 803-810
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3275652
- OpenAlex
- W2050015055
- Cited by
- 176
- References
- 49
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 10 · 2022: 11 · 2021: 9 · 2020: 13 · 2019: 18 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 16 · 2014: 11 · 2013: 15 · 2012: 12
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K99AG040194, K99AG0404184)
- National Institute of Mental Health (MH 083807, R01MH083807)
- National Institute on Drug Abuse (DA027487, R01DA027487)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- wheel running, physical activity, microglia, microglial proliferation, microglial phenotype, neuroinflammation, aging, hippocampus, dentate gyrus, hippocampal neurogenesis, insulin-like growth factor I, neuroprotection
- MeSH terms
- Aging, Animals, Body Weight, Bromodeoxyuridine, Cell Count, Cell Differentiation, Fluorescent Antibody Technique, Hippocampus, Image Processing, Computer-Assisted, Immunohistochemistry, Insulin-Like Growth Factor I, Male, Mice, Inbred BALB C, Neurons, Phenotype, Physical Conditioning, Animal, Running, Microglia, Brain-Derived Neurotrophic Factor, Cell Proliferation, Mice, Neurogenesis
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