The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition
Abstract
We found that a short exercise period enhanced cognitive function on the Morris water maze (MWM), such that exercised animals were significantly better than sedentary controls at learning and recalling the location of the platform. The finding that exercise increased brain-derived neurotrophic factor (BDNF), a molecule important for synaptic plasticity and learning and memory, impelled us to examine whether a BDNF-mediated mechanism subserves the capacity of exercise to improve hippocampal-dependent learning. A specific immunoadhesin chimera (TrkB-IgG), that mimics the BDNF receptor, TrkB, to selectively bind BDNF molecules, was used to block BDNF in the hippocampus during a 1-week voluntary exercise period. After this, a 2-trial-per-day MWM was performed for 5 consecutive days, succeeded by a probe trial 2 days later. By inhibiting BDNF action we blocked the benefit of exercise on cognitive function, such that the learning and recall abilities of exercising animals receiving the BDNF blocker were reduced to sedentary control levels. Inhibiting BDNF action also blocked the effect of exercise on downstream systems regulated by BDNF and important for synaptic plasticity, cAMP response-element-binding protein (CREB) and synapsin I. Specific to exercise, we found an association between CREB and BDNF expression and cognitive function, such that animals who were the fastest learners and had the best recall showed the highest expression of BDNF and associated CREB mRNA levels. These findings suggest a functional role for CREB under the control of BDNF in mediating the exercise-induced enhancement in learning and memory. Our results indicate that synapsin I might also contribute to this BDNF-mediated mechanism.
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In the citing paper
“When the exercise conditions were supplemented with antibodies blocking TrkB, however, the mice had attenuated learning capabilities involving the hippocampus. Furthermore, these mice also lacked synaptic-specific proteins in the hippocampus, thereby demonstrating that BDNF signaling is necessary to allow the benefits of exercise to manifest (Vaynman et al., 2004, 2006).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Vaynman et al., 2004
In the citing paper
“When the exercise conditions were supplemented with antibodies blocking TrkB, however, the mice had attenuated learning capabilities involving the hippocampus. Furthermore, these mice also lacked synaptic-specific proteins in the hippocampus, thereby demonstrating that BDNF signaling is necessary to allow the benefits of exercise to manifest (Vaynman et al., 2004, 2006).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Vaynman et al., 2004
In the citing paper
“Furthermore, BDNF has been shown to be mechanistically linked to exercise-induced improvement in cognitive functions, such as memory and learning (93, 94).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [93]
In the citing paper
“Neurotrophins, in particular the brain-derived neurotrophic factor, may be the common pathway of these mechanisms, may mediate the exercise-driven brain responses and can drive neuronal plasticity, improve cognition, and protect neurons against insult (60–63).”
From The Multidisciplinary Approach to Alzheimer’s Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment (2018) · cites this paper as [61]
In the citing paper
“The importance of BDNF to hippocampal neuroplasticity is epitomized by animal studies, which have found that the manipulation of BDNF expression directly impacts upon performance in spatial and contextual memory tasks (Linnarsson et al., 1997; Alonso et al., 2002; Heldt et al., 2007; Peters et al., 2010), and also that the downregulation of BDNF inhibits AE induced improvements in spatial memory”
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 Vaynman et al., 2004
In the citing paper
“Several studies on both humans and animals show that physical activity, cognitive stimulation, and a balanced diet can stimulate BDNF expression [204–207].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [205]
Citations
Cites
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340
Running enhances neurogenesis, learning, and long-term potentiation in mice
van Praag, H., Christie, B. R., Sejnowski, T. J., & Gage, F. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13427 · Cited by 2,904
The three-dimensional organization of the hippocampal formation: A review of anatomical data
Amaral, D. G., & Witter, M. P. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90424-7 · Cited by 2,180
Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90400-6 · Cited by 1,800
Physical activity and risk of cognitive impairment and dementia in elderly persons
Laurin, D., Verreault, R., Lindsay, J., MacPherson, K., & Rockwood, K. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.498 · Cited by 1,561
Molecular cloning and expression of brain-derived neurotrophic factor
Leibrock, J., Lottspeich, F., Hohn, A., Hofer, M., Hengerer, B., Masiakowski, P., Thoenen, H., & Barde, Y. (1989) · Nature · doi:10.1038/341149a0 · Cited by 1,472
Silva, A. J., Kogan, J. H., Frankland, P. W., & Kida, S. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.127 · Cited by 1,462
Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
Korte, M., Carroll, P., Wolf, E., Brem, G., Thoenen, H., & Bonhoeffer, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8856 · Cited by 1,426
Ageing, fitness and neurocognitive function
Kramer, A. F., Hahn, S., Cohen, N. J., Banich, M. T., McAuley, E., Harrison, C. R., Chason, J., Vakil, E., Bardell, L., Boileau, R. A., et al. (1999) · Nature · doi:10.1038/22682 · Cited by 1,394
Long-Lasting Neurotrophin-Induced Enhancement of Synaptic Transmission in the Adult Hippocampus
Kang, H., & Schuman, E. M. (1995) · Science · doi:10.1126/science.7886457 · Cited by 1,354
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Jha, S., Dong, B. E., Xue, Y., Delotterie, D. F., Vail, M. G., & Sakata, K. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.160 · Cited by 33
Bae, S., Harada, K., Lee, S., Harada, K., Makino, K., Chiba, I., Park, H., & Shimada, H. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051312 · Cited by 29
Palomo, T., Beninger, R. J., Kostrzewa, R. M., & Archer, T. (2008) · Neurotoxicity Research · doi:10.1007/bf03033807 · Cited by 28
Li, A., Yau, S.-Y., Machado, S., Wang, P., Yuan, T.-F., & So, K.-F. (2019) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527318666190308102804 · Cited by 27
Bliss, E. S., Biki, S. M., Wong, R. H. X., Howe, P. R. C., & Mills, D. E. (2023) · European Journal of Applied Physiology · doi:10.1007/s00421-023-05154-y · Cited by 25
Sharma, A. A., & Szaflarski, J. P. (2021) · Epilepsy & Behavior Reports · doi:10.1016/j.ebr.2021.100496 · Cited by 24
Suzuki, W. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.022 · Cited by 17
Brown, B. M., Castalanelli, N., Rainey-Smith, S. R., Doecke, J., Weinborn, M., Sohrabi, H. R., Laws, S. M., Martins, R. N., & Peiffer, J. J. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.01.013 · Cited by 16
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Li, Y., Re, G.-F., Zhao, Y., Kong, D., Mao, J.-H., Wang, K.-H., & Kuang, Y.-Q. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-450 · Cited by 6
Yang, Y. (2025) · Journal of teaching in physical education · doi:10.37766/inplasy2025.3.0111
Metadata
- Authors
- Vaynman, S., Ying, Z., & Gomez‐Pinilla, F.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Ying, Zhe
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-11
- Volume
- 20
- Issue
- 10
- Pages
- 2580-2590
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2119757776
- Cited by
- 1,460
- References
- 70
- Citations by year
- 2026: 49 · 2025: 63 · 2024: 59 · 2023: 62 · 2022: 69 · 2021: 90 · 2020: 75 · 2019: 90 · 2018: 69 · 2017: 107 · 2016: 90 · 2015: 88 · 2014: 93 · 2013: 96 · 2012: 65
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 39522, R01NS045804, NS 045804, R01NS039522)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- physical activity, brain-derived neurotrophic factor, hippocampus, synaptic plasticity, learning and memory, TrkB receptor, CREB, synapsin I, voluntary exercise, Morris water maze, cognitive function
- MeSH terms
- Animals, Behavior, Animal, Cognition, DNA-Binding Proteins, Gene Expression Regulation, Hippocampus, Humans, Immunoglobulin G, Male, Memory, Microspheres, Models, Biological, Motor Activity, Neuronal Plasticity, Physical Conditioning, Animal, Reaction Time, RNA, Messenger, Spatial Behavior, Time Factors, Transcription Factors, Blotting, Western, Synapsins, Rats, Sprague-Dawley, Maze Learning, Brain-Derived Neurotrophic Factor, Reverse Transcriptase Polymerase Chain Reaction, Receptor, trkB, Rats, Activating Transcription Factor 1
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