Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation
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In aged mice, we assessed how intensive exercise affects brain bioenergetics, inflammation, and neurogenesis-relevant parameters. After 8 weeks of a supra-lactate threshold treadmill exercise intervention, 21-month-old C57BL/6 mice showed increased brain peroxisome proliferator-activated receptor gamma coactivator-1α protein, mammalian target of rapamycin and phospho-mammalian target of rapamycin protein, citrate synthase messenger RNA, and mitochondrial DNA copy number. Hippocampal vascular endothelial growth factor A (VEGF-A) gene expression trended higher, and a positive correlation between VEGF-A and PRC messenger RNA levels was observed. Brain doublecortin, brain-derived neurotrophic factor, tumor necrosis factor-α, and CCL11 gene expression, as well as plasma CCL11 protein levels, were unchanged. Despite these apparent negative findings, a negative correlation between plasma CCL11 protein levels and hippocampal doublecortin gene expression was observed; further analysis indicated exercise may mitigate this relationship. Overall, our data suggest supra-lactate threshold exercise activates a partial mitochondrial biogenesis in aged mice, and a gene (VEGF-A) known to support neurogenesis. Our data are consistent with another study that found systemic inflammation in general, and CCL11 protein specifically, suppresses hippocampal neurogenesis. Our study supports the view that intense exercise above the lactate threshold may benefit the aging brain; future studies to address the extent to which exercise-generated lactate mediates the observed effects are warranted.
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Studies in vitro and in animal models suggest that inflammation, especially IL-1β and IFNα, inhibits neurogenesis and reduces exercise-induced neurogenesis.
“Studies conducted both in vitro and in animal models suggest that inflammation in general, and IL-1β and IFNα in particular, inhibit neurogenesis and reduce the magnitude of neurogenesis that is normally induced by exercise”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [288]
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- Authors
- E, L., Burns, J. M., & Swerdlow, R. H.
- Affiliations
- University of Kansas (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Swerdlow, Russell H.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 35
- Issue
- 11
- Pages
- 2574-2583
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4171347
- OpenAlex
- W2036466453
- Cited by
- 106
- References
- 43
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 18 · 2020: 14 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 6 · 2015: 4 · 2014: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Kansas Alzheimer's Disease Center (P30 AG035982)
- Mabel Woodyard Fellowship Award
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- high-intensity exercise, brain aging, mitochondrial biogenesis, neurogenesis, systemic inflammation, eotaxin, VEGF-A, PGC-1α, mTOR, mitochondrial DNA copy number, citrate synthase, hippocampus, doublecortin, brain-derived neurotrophic factor, TNF-α, lactate threshold, treadmill exercise, aged mice
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Doublecortin Domain Proteins, Aging, Animals, Organelle Biogenesis, Brain, Citrate (si)-Synthase, DNA, Mitochondrial, Hippocampus, Humans, Inflammation, Lactates, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Mitochondria, Neuropeptides, Physical Conditioning, Animal, RNA, Messenger, Transcription Factors, Gene Dosage, Vascular Endothelial Growth Factor A, Chemokine CCL11, Neurogenesis, TOR Serine-Threonine Kinases
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