Little Exercise, Big Effects: Reversing Aging and Infection-Induced Memory Deficits, and Underlying Processes
Open accessAbstract
We have previously found that healthy aged rats are more likely to suffer profound memory impairments following a severe bacterial infection than are younger adult rats. Such a peripheral challenge is capable of producing a neuroinflammatory response, and in the aged brain this response is exaggerated and prolonged. Normal aging primes, or sensitizes, microglia, and this appears to be the source of this amplified inflammatory response. Among the outcomes of this exaggerated neuroinflammatory response are impairments in synaptic plasticity and reductions of brain-derived neurotrophic factor (BDNF), both of which have been associated with cognitive impairments. Since it has been shown that physical exercise increases BDNF mRNA in the hippocampus, the present study examined voluntary exercise in 24-month-old F344×BN rats as a neuroprotective therapeutic in our bacterial infection model. Although aged rats ran only an average of 0.7 km per week, this small amount of exercise was sufficient to completely reverse infection-induced impairments in hippocampus-dependent long-term memory compared with sedentary animals. Strikingly, exercise prevented the infection-induced exaggerated neuroinflammatory response and the blunted BDNF mRNA induction seen in the hippocampus of sedentary rats. Moreover, voluntary exercise abrogated age-related microglial sensitization, suggesting a possible mechanism for exercise-induced neuroprotection in aging.
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A consequence of microglia priming in aging is an increased reactivity to peripheral immune challenge.
“A consequence of microglia priming in aging is an increased reactivity to peripheral immune challenge (Barrientos et al, 2011;Frank et al, 2010;Sierra et al, 2007).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Aerobic exercise in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation (Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Exercise prevents microglia priming in aged rats.
“The same study also demonstrated that exercise prevents microglia priming in aged rats.”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
In aged rats, exercise prevented learning impairments following peripheral immune challenge, and this effect was associated with increased expression of hippocampal BDNF.
“In aged rats, exercise prevented learning impairments following peripheral immune challenge, and this effect was associated with increased expression of hippocampal BDNF (Barrientos et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Hippocampal IL-1β levels were reduced in old runners, but not in old sedentary rats.
“For example, hippocampal IL-1β levels were reduced in old runners, but not in old sedentary rats.”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Microglia from runner rats had lower IL-1β, TNFα, and IL-6 mRNA following ex vivo LPS challenge.
“Microglia from runner rats also had lower IL-1β, TNFα, and IL-6 mRNA following ex vivo LPS challenge (Barrientos et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Aerobic exercise in humans is associated with increased hippocampal BDNF.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Aerobic exercise in humans is associated with improved learning and memory.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Aerobic exercise in humans is associated with enhanced neurogenesis.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Voluntary running in rodents is associated with improved learning and memory.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Voluntary running in rodents is associated with enhanced neurogenesis.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Aerobic exercise in humans is associated with dampened inflammatory response to immune challenge and microglia proliferation.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Voluntary running in rodents is associated with increased hippocampal BDNF.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
Voluntary running in rodents is associated with dampened inflammatory response to immune challenge and microglia proliferation.
“Clinical and animal reports show that aerobic exercise (right) in humans and voluntary running in rodents is associated with enhanced neurogenesis, improved learning and memory, increased hippocampal BDNF, and dampened inflammatory response to immune challenge and microglia proliferation(Barrientos et al, 2011;Colcombe et al, 2003;Gebara et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Barrientos et al, 2011
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- Authors
- Barrientos, R. M., Frank, M. G., Crysdale, N. Y., Chapman, T. R., Ahrendsen, J. T., Day, H. E. W., Campeau, S., Watkins, L. R., Patterson, S. L., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-08-10
- Volume
- 31
- Issue
- 32
- Pages
- 11578-11586
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3171131
- OpenAlex
- W2088101528
- Cited by
- 148
- References
- 46
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 11 · 2019: 13 · 2018: 5 · 2017: 9 · 2016: 10 · 2015: 17 · 2014: 15 · 2013: 18 · 2012: 11
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG02827, R01AG028271, R21AG031467)
- 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
- voluntary exercise, neuroinflammation, aging, bacterial infection, memory impairment, hippocampus, brain-derived neurotrophic factor, synaptic plasticity, neuroprotection, long-term memory, sedentary behavior
- MeSH terms
- Aging, Animals, Escherichia coli Infections, Exercise Test, Hippocampus, Male, Memory Disorders, Physical Conditioning, Animal, Rats, Inbred BN, Rats, Inbred F344, Rats
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