Physical activity for the promotion of cognitive functions: The role of the exercise-induced Brain Derived Neurotrophic Factor in muscle-brain crosstalk

Titolo Rivista RIVISTA DI STUDI SULLA SOSTENIBILITA'
Autori/Curatori Mariarosa Masullo, Nounagnon F. Agbangla, Rosaria Arcone
Anno di pubblicazione 2025 Fascicolo 2025/1Suppl.
Lingua Inglese Numero pagine 12 P. 23-34 Dimensione file 0 KB
DOI 10.3280/riss2025oa19843
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During physical activity, the contracting skeletal muscle acts as an endocrine organ for its ability to secrete molecules called myokines, mostly cytokines and growth factors, which modulate metabolic and cellular functions in different organs and tissues. Some of the most relevant for the brain include Brain-Derived Neurotrophic Factor, Insulin-like growth factor-1, Interleukin-6, Irisin, cathepsin B, and vascular endothelial growth factor, which are involved in muscle-brain crosstalk. Brain-Derived Neurotrophic Factor improves cognitive functions by neurogenesis, and the increase of plasticity in the hippocampus region. This review aims to provide recent insights on the role played by physical activity and diet in ameliorating cognitive functions, focusing on the effects involving Brain-Derived Neurotrophic Factor.

During physical activity, the contracting skeletal muscle acts as an endocrine organ for its ability to secrete molecules called myokines, mostly cytokines and growth factors, which modulate metabolic and cellular functions in different organs and tissues. Some of the most relevant for the brain include Brain-Derived Neurotrophic Factor, Insulin-like growth factor-1, Interleukin-6, Irisin, cathepsin B, and vascular endothelial growth factor, which are involved in muscle-brain crosstalk. Brain-Derived Neurotrophic Factor improves cognitive functions by neurogenesis, and the increase of plasticity in the hippocampus region. This review aims to provide recent insights on the role played by physical activity and diet in ameliorating cognitive functions, focusing on the effects involving Brain-Derived Neurotrophic Factor.

Parole chiave:; Physical activity; Cognitive functions; Myokines; Brain-derived neurotrophic factor (BDNF); Muscle-brain crosstalk; Neurodegenerative disorders

  1. Agnew-Blais J.C., Wassertheil-Smoller S., Kang J.H. et al. (2015). Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women's Health Initiative Memory Study. J. Acad. Nutr. Diet., 115(2): 231-241. DOI: 10.1016/j.jand.2014.07.006.
  2. Akalp K., Ferreira J.P., Soares C.M., Ribeiro M.J., Teixeira A.M. (2024). The effects of different types of exercises on cognition in older persons with mild cognitive impairment: A systematic review and meta-analysis. Arch. Gerontol. Geriatr., 126, 105541. DOI: 10.1016/j.archger.2024.105541.
  3. Arazi H., Babaei P., Moghimi M., Asadi A. (2021). Acute effects of strength and endurance exercise on serum BDNF and IGF-1 levels in older men. BMC geriatrics, 21(1): 50. DOI: 10.1186/s12877-020-01937-6.
  4. Arcone R., D’Errico A., Nasso R. et al. (2023). Inhibition of Enzymes Involved in Neurodegenerative Disorders and Aβ1-40 Aggregation by Citrus limon Peel Polyphenol Extract. Molecules, 28(17), 6332. DOI: 10.3390/molecules28176332.
  5. Baker L.D., Frank L.L., Foster-Schubert K. et al. (2010). Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch. Neurol., 67(1): 71-79. DOI: 10.1001/archneurol.2009.307.
  6. Bortoluzzi S., Scannapieco P., Cestaro A., Danieli G.A., and Schiaffino S. (2006). Computational reconstruction of the human skeletal muscle secretome. Proteins, 62(3): 776-792. DOI: 10.1002/prot.20803.
  7. Brigadski T., Leßmann V. (2020). The physiology of regulated BDNF release. Cell Tissue Res., 382: 15-45. DOI: 10.1007/s00441-020-03253-2.
  8. Cefis M., Quirié A., Pernet N., Marie C., Garnier P., Prigent-Tessier A. (2020). Brain-derived neurotrophic factor is a full endothelium-derived factor in rats. Vasc. Pharmacol., 106674. DOI: 10.1016/j.vph.2020.106674.
  9. Chieffi S., Messina G., Villano I., Messina A., Valenzano A., Moscatelli F., Salerno M., Sullo A., Avola R., Monda V., Cibelli G., and Monda M. (2017). Neuroprotective Effects of Physical Activity: Evidence from Human and Animal Studies. Frontiers in Neurology, 8, 188. DOI: 10.3389/fneur.2017.00188.
  10. Coelho F.G., Vital T.M., Stein A.M., Arantes F.J., Rueda A.V., Camarini R., Teodorov E., Santos-Galduróz R.F. (2014). Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer’s disease. J. Alzheimers dis., 39(2): 401-408. DOI: 10.3233/JAD-131073.
  11. Davis M.A., Chang C.H., Simonton S., Bynum J.P.W. (2022). Trends in US medicare decedents’ diagnosis of dementia from 2004 to 2017. JAMA Health Forum, 3, e220346. DOI: 10.1001/jamahealthforum.2022.0346.
  12. D’Errico A., Nasso R., Rullo R., Maiuolo J., Costanzo P., Bonacci S., Oliverio M., De Vendittis E., Masullo M., Arcone R. (2024). Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage. Molecules, 29, DOI: 10.3390/molecules29020548.
  13. Dinoff A., Herrmann N., Swardfager W., et al. (2016) The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis. PLoS One, 11(9), e0163037. DOI: 10.1371/journal.pone.0163037.
  14. Edelmann E., Lessmann V., Brigadski T. (2014). Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity. Neuropharmacology, 76, Pt C: 610-627. DOI: 10.1016/j.neuropharm.2013.05.043.
  15. Erickson K.I., Hillman C., Stillman C.M., et al. (2019). Physical Activity, Cognition, and Brain Outcomes: A Review of the 2018 Physical Activity Guidelines. Med. Sci. Sports. Exerc., 51(6): 1242-1251. DOI: 10.1249/MSS.0000000000001936.
  16. Erickson K.I., Voss M.W., Prakash R.S., Basak C., Szabo A., Chaddock L., Kim J.S., Heo S., Alves H., White S.M., Wojcicki T.R., Mailey E., Vieira V.J., Martin S.A., Pence B.D., Woods J.A., McAuley E., Kramer A. F. (2011). Exercise training increases size of hippocampus and improves memory. Proc. Natl. Acad. Sci. USA, 108(7): 3017-3022. DOI: 10.1073/pnas.1015950108.
  17. Fekete M., Varga P., Ungvari Z. et al. (2025). The role of the Mediterranean diet in reducing the risk of cognitive impairement, dementia, and Alzheimer’s disease: a meta-analysis. Geroscience, Published online January 11. DOI: 10.1007/s11357-024-01488-3.
  18. Fu J., Tan L.J., Lee J.E., Shin S. (2022). Association between the mediterranean diet and cognitive health among healthy adults: A systematic review and meta-analysis, Front. Nutr., 9, 946361. DOI: 10.3389/fnut.2022.946361.
  19. Gass P. and Hellweg R. (2010). Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker for affective disorders?. Int. J. Neuropsychopharmacology, 13(1): 1-4. DOI: 10.1017/S1461145709991039.
  20. Grabska-Kobyłecka I., Szpakowski P., Król A. et al. (2023). Polyphenols and Their Impact on the Prevention of Neurodegenerative Diseases and Development. Nutrients, 15(15), 3454. DOI: 10.3390/nu15153454.
  21. Gravesteijn E., Mensink R.P., Plat J. (2022). Effects of nutritional interventions on BDNF concentrations in humans: a systematic review, Nutr. Neurosci., 25(7): 1425-1436. DOI: 10.1080/1028415X.2020.1865758.
  22. Hernández-Del Caño C., Varela-Andrés N., Cebrián-León A., Deogracias R. (2024). Neurotrophins and Their Receptors: BDNF’s Role in GABAergic Neurodevelopment and Disease. Int. J. Mol. Sci., 25(15), 8312. DOI: 10.3390/ijms25158312.
  23. Hock C., Heese K., Hulette C., Rosenberg C., Otten U. (2000). Region-specific neurotrophin imbalances in Alzheimer disease: Decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch. Neurol., 57: 846-851. DOI: 10.1001/archneur.57.6.846.
  24. Iizuka K., Machida T., Hirafuji M. (2014). Skeletal muscle is an endocrine organ, J. Pharmacol. Sci., 125(2): 125-131. DOI: 10.1254/jphs.14r02cp.
  25. Jalouli M., Rahman M.A., Biswas P. et al. (2025). Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: a comprehensive review. Front. Pharmacol., 16, 1492517. DOI: 10.3389/fphar.2025.1492517.
  26. Kekäläinen T., Luchetti M., Terracciano A. et al. (2023). Physical activity and cognitive function: moment-to-moment and day-to-day associations. Int. J. Behav. Nutr. Phys. Act., 20(1): 137. DOI: 10.1186/s12966-023-01536-9.
  27. Koshimizu H., Kiyosue K., Hara T. (2009) et al. Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival. Mol. Brain, 2, 27. DOI: 10.1186/1756-6606-2-27.
  28. Leal G., Comprido D., Duarte C.B. (2014). BDNF-induced local protein synthesis and synaptic Plasticity. Neuropharmacology, 76, Pt C: 639-656. DOI: 10.1016/j.neuropharm.2013.04.005.
  29. Lee J. H., and Jun H. S. (2019). Role of Myokines in Regulating Skeletal Muscle Mass and Function. Front. Physiol., 10, 42. DOI: 10.3389/fphys.2019.00042.
  30. Liu P.Z., Nusslock R. (2018). Exercise-Mediated Neurogenesis in the Hippocampus via BDNF. Front. Neurosci., 12, 52. DOI: 10.3389/fnins.2018.00052.
  31. Maiuolo J., Costanzo P., Masullo M., D’Errico A., Nasso R., Bonacci S., Mollace V., Oliverio M., Arcone R. (2023). Hydroxytyrosol-Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells. Int. J. Mol. Sci., 24, 13461. DOI: 10.3390/ijms241713461.
  32. Marie C., Pedard M., Quirié A. et al. (2018). Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function?. J. Cer. Blood Flow Metabolism, 38(6): 935-949. DOI: 10.1177/0271678X18766772.
  33. Matsumoto T., Rauskolb S., Polack M. et al. (2008). Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF. Nat. Neurosci., 11(2): 131-133. DOI: 10.1038/nn2038.
  34. Montesano P., Tafuri D., Mazzeo F. (2013). Improvement of the motor performance difference in athletes of weelchair Basketball. J. Phys. Educ. Sport, 13(3): 362-370. DOI: 10.7752/jpes.2013.03058.
  35. Miculas D.C., Negru P.A., Bungau S.G., Behl T., Hassan S.S., Tit D.M. (2023). Pharmacotherapy evolution in alzheimer’s disease: Current framework and relevant directions. Cells, 12(1): 131-226. DOI: 10.3390/cells12010131.
  36. Miranda M., Moric J.F., Zanoni, M.B., Bekinschtein P. (2019). Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Front. Cell. Neurosci., 13, 363. DOI: 10.3389/fncel.2019.00363.
  37. Narisawa-Saito M., Wakabayashi K., Tsuji S., Takahashi H., Nawa H. (1996). Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer’s disease. Neuroreport, 7: 2925-2928. DOI: 10.1097/00001756-199611250-00024.
  38. Nasso R., D’Errico A., Motti M.L., Masullo M., Arcone R. (2024). Dietary Protein and Physical Exercise for the Treatment of Sarcopenia. Clin. Pract., 14: 1451-1467. DOI: 10.3390/clinpract14040117.
  39. Nazlieva N., Mavilidi M.F., Baars M., Paas F. (2019). Establishing a Scientific Consensus on the Cognitive Benefits of Physical Activity. Int. J. Environ. Res. Public Health, 17(1), 29. DOI: 10.3390/ijerph17010029.
  40. Nicastri C.M., McFeeley B.M., Simon S.S et al. (2022). BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults. Alzheimers Dement (N Y), 8(1), e12337. DOI: 10.1002/trc2.12337.
  41. Pan W., Banks W.A., Fasold M.B., Bluth J., Kastin A.J. (1998). Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology, 37(12): 1553-1561. DOI: 10.1016/s0028-3908(98)00141-5.
  42. Pedersen B.K., and Febbraio M.A. (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol., 8(8): 457-465. DOI: 10.1038/nrendo.2012.49.
  43. Román GC., Jackson R.E., Gadhia R., Román A.N., Reis J. (2019). Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease. Rev. Neurol. (Paris), 175: 724-741. DOI: 10.1016/j.neurol.2019.08.005.
  44. Sanaeifar F., Pourranjbar S., Pourranjbar M. et al. (2024). Beneficial effects of physical exercise on cognitive-behavioral impairments and brain-derived neurotrophic factor alteration in the limbic system induced by neurodegeneration. Exp. Gerontol., 195, 112539. DOI: 10.1016/j.exger.2024.112539.
  45. Sasi M., Vignoli B., Canossa M., Blum R. (2017). Neurobiology of local and intercellular BDNF signaling. Pflugers Archiv, 469(5-6): 593-610. DOI: 10.1007/s00424-017-1964-4.
  46. Schmolesky M.T., Webb D.L., Hansen R.A. (2013). The effects of aerobic exercise intensity and duration on levels of brain-derived neurotrophic factor in healthy men. J. Sports Sci. Med., 12(3): 502-511.
  47. Severinsen M.C.K. (2020). Pedersen BK. Muscle-Organ Crosstalk: The Emerging Roles of Myokines [published correction appears in Endocr Rev. 2021 Jan 28; 42(1): 97-99. DOI: 10.1210/endrev/bnaa024.]. Endocr Rev., 41(4): 594-609. doi: 10.1210/endrev/bnaa016.
  48. Szuhany K.L., Bugatti M., Otto M.W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res., 60: 56-64. DOI: 10.1016/j.jpsychires.2014.10.003.
  49. Tirani S.A., Poursalehi D., Lotfi K. et al. (2024). Adherence to Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay Diet in Relation to Serum Brain-Derived Neurotrophic Factor Concentrations and Metabolic Health Status in Adults. Curr. Dev. Nutr. 8, 102082. DOI: 10.1016/j.cdnut.2024.102082.
  50. Tremblay M. S., Aubert S., Barnes J. D., Saunders T. J., Carson V., Latimer-Cheung A. E. et al., (2017). Sedentary behavior research network (SBRN) - terminology consensus project process and outcome. Int. J. Behav. Nutr. Phys. Act,. 14: 75. DOI: 10.1186/S12966-017-0525-8.
  51. Vints W.A.J., Gökçe E., Langeard A. et al. (2023). Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis. Front. Aging Neurosci., 15: 1213057. DOI: 10.3389/fnagi.2023.1213057.
  52. Wesnes K.A., Aarsland D., Ballard C., Londos E. (2015) Memantine improves attention and episodic memory in Parkinson’s disease dementia and dementia with Lewy bodies, Int. J. Geriatr. Psychiatry, 30: 46-54.
  53. Wrann C.D., White J.P., Salogiannnis J., Laznik-Bogoslavski D., Wu J., Ma D., Lin J.D., Greenberg M.E., Spiegelman B.M. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 18(5): 649-659. DOI: 10.1016/j.cmet.2013.09.008.
  54. Xu Lou I., Chen J., Ali K., Shaikh A.L., Chen Q. (2023). Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials. Front Pharmacol., 14. 1190604. DOI: 10.3389/fphar.2023.1190604.
  55. Zhao Y., Li Y., Wang L., Song Z., Di,T., Dong X. et al. (2022). Physical activity and cognition in sedentary older adults: A systematic review and meta-analysis. J. Alzheimers Dis., 87: 957-968. DOI: 10.3233/JAD-220073.
  56. Ziaei S., Mohammadi S., Hasani M. et al. (2024). A systematic review and meta-analysis of the omega-3 fatty acids effects on brain-derived neurotrophic factor (BDNF). Nutr. Neurosci., 27: 715-725. DOI: 10.1080/1028415X.2023.2245996.
  57. Zuccato C., Marullo M., Conforti P., MacDonald M.E., Tartari M., Cattaneo E. (2008). Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington’s disease. Brain Pathol., 18: 225-238. DOI: 10.1111/j.1750-3639.2007.00111.xxs.

Mariarosa Masullo, Nounagnon F. Agbangla, Rosaria Arcone, Physical activity for the promotion of cognitive functions: The role of the exercise-induced Brain Derived Neurotrophic Factor in muscle-brain crosstalk in "RIVISTA DI STUDI SULLA SOSTENIBILITA'" 1Suppl./2025, pp 23-34, DOI: 10.3280/riss2025oa19843