Functional analysis of neurovascular adaptations to exercise in the dentate gyrus of young adult mice associated with cognitive gain.
Open accessAbstract
The discovery that aerobic exercise increases adult hippocampal neurogenesis and can enhance cognitive performance holds promise as a model for regenerative medicine. This study adds two new pieces of information to the rapidly growing field. First, we tested whether exercise increases vascular density in the granular layer of the dentate gyrus, whole hippocampus, and striatum in C57BL/6J mice known to display procognitive effects of exercise. Second, we determined the extent to which new neurons from exercise participate in the acute neuronal response to high levels of running in B6D2F1/J (F1 hybrid of C57BL/6J female by DBA/2J male). Mice were housed with or without a running wheel for 50 days (runner vs. sedentary). The first 10 days, they received daily injections of BrdU to label dividing cells. The last 10 days, mice were tested for performance on the Morris water maze and rotarod and then euthanized to measure neurogenesis, c-Fos induction from running and vascular density. In C57BL/6J, exercise increased neurogenesis, density of blood vessels in the dentate gyrus and striatum (but not whole hippocampus), and enhanced performance on the water maze and rotarod. In B6D2F1/J, exercise also increased hippocampal neurogenesis but not vascular density in the granular layer. Improvement on the water maze from exercise was marginal, and no gain was seen for rotarod, possibly because of a ceiling effect. Running increased the number of c-Fos positive neurons in the granular layer by fivefold, and level of running was strongly correlated with c-Fos within 90 min before euthanasia. In runners, approximately 3.3% (+/-0.008 S.E.) of BrdU-positive neurons in the middle of the granule layer displayed c-Fos when compared with 0.8% (+/-0.001) of BrdU-negative neurons. Results suggest that procognitive effects of exercise are associated with increased vascular density in the dentate gyrus and striatum in C57BL/6J mice, and that new neurons from exercise preferentially function in the neuronal response to running in B6D2F1/J.
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Inhibiting the rate of cell proliferation in mice blocked aerobic exercise-induced improvements in spatial memory performance.
“For example, inhibiting the rate of cell proliferation in mice was sufficient to impair pattern separation (Deng et al., 2010) and block AE-induced improvements in spatial (Clark et al., 2009) and contextual (Wojtowicz et al., 2008) memory performance, but only in conditions in which the task required fine spatial discriminations (i.e., where pattern separation was necessary; Creer et al., 2010).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Clark et al., 2009
VEGF facilitates vascularization, particularly within the dentate gyrus (DG), and thereby supports AE-induced stimulation of neurogenesis.
“By facilitating vascularization in this way, particularly within the DG (Clark et al., 2009), the molecule also supports the AE induced stimulation of neurogenesis (Gomez-Pinilla and Hillman, 2013).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Clark et al., 2009
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“…the rate of cell proliferation in mice was sufficient to impair pattern separation (Deng et al., 2010) and block AE-induced improvements in spatial (Clark et al., 2009) and contextual (Wojtowicz et al., 2008) memory performance, but only in conditions in which the task required fine spatial…”
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- Authors
- Clark, P. J., Brzezinska, W. J., Puchalski, E. K., Krone, D. A., & Rhodes, J. S.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Rhodes, Justin S.
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2009-01-08
- Volume
- 19
- Issue
- 10
- Pages
- 937-950
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- PMC
- PMC2791165
- OpenAlex
- W2011495546
- Cited by
- 138
- References
- 49
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 5 · 2017: 12 · 2016: 11 · 2015: 10 · 2014: 12 · 2013: 7 · 2012: 16
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH083807)
- National Institute on Drug Abuse (R01DA027487)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- aerobic exercise, adult hippocampal neurogenesis, dentate gyrus, vessel density, c-fos, running wheel, cognitive enhancement, striatum, BrdU labeling, C57BL/6J mice, Morris water maze, rotarod test, granular layer
- MeSH terms
- Animals, Cognition, Corpus Striatum, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Motor Activity, Neurons, Physical Conditioning, Animal, Running, Species Specificity, Time Factors, Maze Learning, Dentate Gyrus, Neovascularization, Physiologic, Mice, Neurogenesis
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