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Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms
Abstract
A growing body of scientific evidence indicates that exercise has a positive impact on human health, including neurological health. Aerobic exercise, which is supposed to enhance cardiovascular functions and metabolism, also induces neurotrophic factors that affect hippocampal neurons, thereby improving spatial learning and memory. Alternatively, little is known about the effect of resistance exercise on hippocampus-dependent memory, although this type of exercise is increasingly recommended to improve muscle strength and bone density and to prevent age-related disabilities. Therefore, we evaluated the effects of resistance training on spatial memory and the signaling pathways of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing these effects with those of aerobic exercise. Adult male Wistar rats underwent 8 weeks of aerobic training on a treadmill (AERO group) or resistance training on a vertical ladder (RES group). Control and sham groups were also included. After the training period, both AERO and RES groups showed improved learning and spatial memory in a similar manner. However, both groups presented distinct signaling pathways. Although the AERO group showed increased level of IGF-1, BDNF, TrkB, and β-CaMKII (calcium/calmodulin-dependent kinase II) in the hippocampus, the RES group showed an induction of peripheral and hippocampal IGF-1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the hippocampus. These distinct pathways culminated in an increase of synapsin 1 and synaptophysin expression in both groups. These findings demonstrated that both aerobic and resistance exercise can employ divergent molecular mechanisms but achieve similar results on learning and spatial memory.
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“partly because it increases IGF-1 levels [172] and reduces inflammation [173] during training”
From Comparative Effectiveness of Multiple Exercise Interventions in the Treatment of Mental Health Disorders: A Systematic Review and Network Meta-Analysis (2022) · cites this paper as [172]
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“(Neepser et al., 1995; Liu-Ambrose et al., 2010; Cassilhas et al., 2012).”
Guo, Z., Dong, L., Lin, J., Duan, Y., Liu, W., Jiang, W., Liu, C., Jia, S., Song, Y., Ding, F., et al. (2026) · European Journal of Sport Science · doi:10.1002/ejsc.70272
“By systematically combining modalities, CT primarily yields profound synergistic effects, simultaneously activating the aerobic‐driven BDNF‐TrkB cascade and the resistance‐driven IGF‐1‐Akt neurotrophic pathways (Cassilhas et al. 2012).”
López, Á., & Jesús, M. (2015) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Metadata
- Authors
- Cassilhas, R. C., Lee, K. S., Fernandes, J., Oliveira, M. G. M., Tufik, S., Meeusen, R., & de Mello, M. T.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Vrije Universiteit Brussel (BE)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 202
- Pages
- 309-317
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2146864294
- Cited by
- 394
- References
- 74
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 26 · 2023: 34 · 2022: 26 · 2021: 36 · 2020: 34 · 2019: 35 · 2018: 34 · 2017: 23 · 2016: 28 · 2015: 23 · 2014: 21 · 2013: 15 · 2012: 8
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- São Paulo Research Foundation (2008/03083-6)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- spatial memory, aerobic exercise, resistance training, hippocampus, brain-derived neurotrophic factor, insulin-like growth factor I, IGF-1 receptor, Akt signaling, TrkB, CaMKII, synapsin-1, synaptophysin, neurotrophic factors, exercise and cognition
- MeSH terms
- Animals, Corticosterone, Enzyme-Linked Immunosorbent Assay, Hippocampus, Insulin-Like Growth Factor I, Male, Memory, Physical Conditioning, Animal, Radioimmunoassay, Space Perception, Blotting, Western, Signal Transduction, Synapsins, Rats, Wistar, Receptor, IGF Type 1, Maze Learning, Brain-Derived Neurotrophic Factor, Receptor, trkB, Oncogene Protein v-akt, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Resistance Training
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