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Review
. 2021 Aug 16;22(16):8814.
doi: 10.3390/ijms22168814.

The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4/5: A Review

Daniel Ribeiro  1   2   3 , Luca Petrigna  4 , Frederico C Pereira  2   3   5 , Antonella Muscella  6 , Antonino Bianco  4 , Paula Tavares  1   2   3
Affiliations
Review

The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4/5: A Review

Daniel Ribeiro et al. Int J Mol Sci. .

Abstract

(1) Background: One mechanism through which physical activity (PA) provides benefits is by triggering activity at a molecular level, where neurotrophins (NTs) are known to play an important role. However, the expression of the circulating levels of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4/5), in response to exercise, is not fully understood. Therefore, the aim was to provide an updated overview on the neurotrophin (NT) variation levels of BDNF and NT-4/5 as a consequence of a long-term aerobic exercise intervention, and to understand and describe whether the upregulation of circulating NT levels is a result of neurotrophic factors produced and released from the brain, and/or from neurotrophic secreting peripheral organs. (2) Methods: The articles were collected from PubMed, SPORTDiscus, Web of Science, MEDLINE, and Embase. Data were analyzed through a narrative synthesis. (3) Results: 30 articles studied humans who performed training protocols that ranged from 4 to 48 weeks; 22 articles studied rodents with an intervention period that ranged from 4 to 64 weeks. (4) Conclusions: There is no unanimity between the upregulation of BDNF in humans; conversely, concerning both BDNF and NT-4/5 in animal models, the results are heterogeneous. Whilst BDNF upregulation appears to be in relative agreement, NT-4/5 seems to display contradictory and inconsistent conclusions.

Keywords: brain-derived neurotrophic factor; exercise; neurotrophin-4; neurotrophins; peripheral circulation.

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Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Figure 1
Figure 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart.
See this image and copyright information in PMC

References

    1. Dishman R.K., Berthoud H.R., Booth F.W., Cotman C.W., Edgerton V.R., Fleshner M.R., Gandevia S.C., Gomez-Pinilla F., Greenwood B.N., Hillman C.H., et al. Neurobiology of exercise. Obesity (Silver Spring) 2006;14:345–356. doi: 10.1038/oby.2006.46. - DOI - PubMed
    1. Zoladz J.A., Pilc A. The effect of physical activity on the brain derived neurotrophic factor: From animal to human studies. J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc. 2010;61:533–541. - PubMed
    1. Zembron-Lacny A., Dziubek W., Rynkiewicz M., Morawin B., Woźniewski M. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men. Braz. J. Med. Biol. Res. 2016;49 doi: 10.1590/1414-431x20165253. - DOI - PMC - PubMed
    1. Knaepen K., Goekint M., Heyman E.M., Meeusen R. Neuroplasticity–exercise-induced response of peripheral brain-derived neurotrophic factor: A systematic review of experimental studies in human subjects. Sports Med. 2010;40:765–801. doi: 10.2165/11534530-000000000-00000. - DOI - PubMed
    1. Cotman C.W., Berchtold N.C., Christie L.-A. Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30:464–472. doi: 10.1016/j.tins.2007.06.011. - DOI - PubMed