Exercise-Induced Neuroplasticity: Mechanisms Underlying Hippocampal Growth and Cognitive Enhancement
DOI:
https://doi.org/10.64229/108srm39Keywords:
Exercise, Neuroplasticity, Hippocampus, BDNF, IGF-1, Cognitive FunctionAbstract
Regular physical exercise has emerged as a potent non-pharmacological approach to promoting brain health, delaying cognitive decline, and counteracting neurodegenerative processes. In particular, aerobic training enhances hippocampal neuroplasticity by stimulating neurogenesis, angiogenesis, synaptic remodeling, and volumetric growth. These adaptations are largely mediated by neurotrophins such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), which together orchestrate neuronal survival, synaptic potentiation, and the formation of new circuits. In animal models, exercise-induced elevations of BDNF and IGF-1 correlate with increased neurogenesis in the dentate gyrus and structural expansion of the hippocampus. Human studies complement these findings, showing that sustained aerobic training can enlarge hippocampal volume and improve episodic memory. Beyond molecular mediators, exercise also triggers systemic changes through muscle-derived exerkines (e.g., irisin, lactate), which amplify neurotrophic signaling in the brain. This study investigated the impact of treadmill running on hippocampal neurobiology and cognition in rats, combining biochemical assays, volumetric MRI, and behavioral testing. Results revealed significant increases in BDNF, IGF-1, neurogenesis, hippocampal volume, and spatial memory, supporting the hypothesis that exercise-induced neuroplasticity underlies cognitive enhancement. These findings highlight exercise as a powerful intervention to preserve hippocampal integrity across the lifespan and suggest potential biomarkers for monitoring brain health.
References
[1]Balbim, G. M., Boa Sorte Silva, N. C., Ten Brinke, L., Falck, R. S., Hortobágyi, T., Granacher, U., ... & Liu-Ambrose, T. (2024). Aerobic exercise training effects on hippocampal volume in healthy older individuals: a meta-analysis of randomized controlled trials. Geroscience, 46(2), 2755-2764.
[2]Cefis, M., Chaney, R., Wirtz, J., Méloux, A., Quirié, A., Leger, C., ... & Garnier, P. (2023). Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction. Frontiers in molecular neuroscience, 16, 1275924.
[3]Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., ... & Kramer, A. F. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the national academy of sciences, 108(7), 3017-3022.
[4]He, Y., Wang, Q., Wu, H., Dong, Y., Peng, Z., Guo, X., & Jiang, N. (2023). The role of IGF-1 in exercise to improve obesity-related cognitive dysfunction. Frontiers in Neuroscience, 17, 1229165.
[5]Johnson, R. A., Rhodes, J. S., Jeffrey, S. L., Garland Jr, T., & Mitchell, G. S. (2003). Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience, 121(1), 1-7.
[6]Tsao, C. H., Flint, J., & Huang, G. J. (2022). Influence of diurnal phase on behavioral tests of sensorimotor performance, anxiety, learning and memory in mice. Scientific reports, 12(1), 432.
[7]Kraemer, R. R., & Kraemer, B. R. (2023). The effects of peripheral hormone responses to exercise on adult hippocampal neurogenesis. Frontiers in Endocrinology, 14, 1202349.
[8]Sidorova, M., Kronenberg, G., Matthes, S., Petermann, M., Hellweg, R., Tuchina, O., ... & Klempin, F. (2021). Enduring effects of conditional brain serotonin knockdown, followed by recovery, on adult rat neurogenesis and behavior. Cells, 10(11), 3240.
[9]Gazula, H., Tregidgo, H. F., Billot, B., Balbastre, Y., Williams-Ramirez, J., Herisse, R., ... & Iglesias, J. E. (2024). Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology. Elife, 12, RP91398.
[10]Iglesias, J. E., Billot, B., Balbastre, Y., Magdamo, C., Arnold, S. E., Das, S., ... & Fischl, B. (2023). SynthSR: A public AI tool to turn heterogeneous clinical brain scans into high-resolution T1-weighted images for 3D morphometry. Science advances, 9(5), eadd3607.
[11]Gao, Y., Syed, M., & Zhao, X. (2023). Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis. Hippocampus, 33(4), 373-390.
[12]Gesmundo, I., Pedrolli, F., Cai, R., Sha, W., Schally, A. V., & Granata, R. (2025). Growth hormone-releasing hormone and cancer. Reviews in Endocrine and Metabolic Disorders, 26(3), 443-456.
[13]Toader, C., Serban, M., Munteanu, O., Covache-Busuioc, R. A., Enyedi, M., Ciurea, A. V., & Tataru, C. P. (2025). From synaptic plasticity to Neurodegeneration: BDNF as a transformative target in medicine. International Journal of Molecular Sciences, 26(9), 4271.
[14]Rhea, E. M., Banks, W. A., & Raber, J. (2022). Insulin resistance in peripheral tissues and the brain: a tale of two sites. Biomedicines, 10(7), 1582.
[15]Arjunan, A., Sah, D. K., Woo, M., & Song, J. (2023). Identification of the molecular mechanism of insulin-like growth factor-1 (IGF-1): a promising therapeutic target for neurodegenerative diseases associated with metabolic syndrome. Cell & Bioscience, 13(1), 16.
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