Updated overview on interplay between physical exercise, neurotrophins, and cognitive function in humans

Giuseppe Lippi, Camilla Mattiuzzi, Fabian Sanchis-Gomar, Giuseppe Lippi, Camilla Mattiuzzi, Fabian Sanchis-Gomar

Abstract

The many important benefits of physical exercise also encompass maintenance or improvement of cognitive functions. Among the various mechanisms underlying the association between physical exercise and brain health, recent evidence attests that neurotrophin receptor signaling may have an important role, because the activation of this pathway leads to growth and differentiation of new neurons and synapses, supports axonal and dendritic growth, fosters synaptic plasticity, and preserves survival of existing neurons. In this review of published evidence, we highlight that a positive relationship exists between physical exercise and circulating brain-derived neurotrophic factor levels and that the postexercise variation of this molecule is associated with improvement of neurocognitive functioning. Less clear evidence has instead been published for other neurotrophins, such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Overall, promotion of adequate volumes and intensities of physical exercise (i.e., approximately 3 months of moderate-intensity aerobic exercise, with 2-3 sessions/week lasting not less than 30 min) may hence be regarded as an inexpensive and safe strategy for boosting brain-derived neurotrophic factor release, thus preserving or restoring cognitive functions.

Keywords: Cognitive function; Neurotrophins; Physical exercise; Sport.

© 2019 Published by Elsevier B.V. on behalf of Shanghai University of Sport.

Figures

Graphical abstract
Graphical abstract

References

    1. Pareja-Galeano H., Mayero S., Sanchis-Gomar F. Exercise, neuroplasticity, and growth factors in adolescence. In: Farooqui TFaAA., editor. Diet and exercise in cognitive function and neurological diseases. Wiley Blackwell; Hoboken, NJ: 2015. pp. 323–337.
    1. Bothwell M. Recent advances in understanding neurotrophin signaling. F1000Res. 2016;5 pii: F1000 Faculty Rev-1885.
    1. Vilar M., Mira H. Regulation of neurogenesis by neurotrophins during adulthood: expected and unexpected roles. Front Neurosci. 2016;10:26.
    1. Huang E.J., Reichardt L.F. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.
    1. Lu B., Nagappan G., Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol. 2014;220:223–250.
    1. Pareja-Galeano H., Brioche T., Sanchis-Gomar F., Montal A., Jovani C., Martinez-Costa C. Impact of exercise training on neuroplasticity-related growth factors in adolescents. J Musculoskelet Neuronal Interact. 2013;13:368–371.
    1. Warburton D.E.R., Bredin S.S.D. Health benefits of physical activity: a systematic review of current systematic reviews. Curr Opin Cardiol. 2017;32:541–556.
    1. Vina J., Sanchis-Gomar F., Martinez-Bello V., Gomez-Cabrera M.C. Exercise acts as a drug; the pharmacological benefits of exercise. Br J Pharmacol. 2012;167:1–12.
    1. Pareja-Galeano H., Mayero S., Perales M., Garatachea N., Santos-Lozano A., Fiuza-Luces C. Biological rationale for regular physical exercise as an effective intervention for the prevention and treatment of depressive disorders. Curr Pharm Des. 2016;22:3764–3775.
    1. Ploughman M. Exercise is brain food: the effects of physical activity on cognitive function. Dev Neurorehabil. 2008;11:236–240.
    1. Lee M.C., Byun K., Kim J.S., Lee H., Kim K. Trends in exercise neuroscience: raising demand for brain fitness. J Exerc Rehabil. 2019;15:176–179.
    1. El-Sayes J., Harasym D., Turco C.V., Locke M.B., Nelson A.J. Exercise-induced neuroplasticity: a mechanistic model and prospects for promoting plasticity. Neuroscientist. 2019;25:65–85.
    1. Pareja-Galeano H., Sanchis-Gomar F., Mayero S. Autism spectrum disorders: possible implications of BDNF modulation through epigenetics. Acta Psychiatr Scand. 2013;128:97.
    1. Premack D. Human and animal cognition: continuity and discontinuity. Proc Natl Acad Sci U S A. 2007;104:13861–13867.
    1. Sherwood C.C., Subiaul F., Zawidzki T.W. A natural history of the human mind: tracing evolutionary changes in brain and cognition. J Anat. 2008;212:426–454.
    1. Szuhany K.L., Bugatti M., Otto M.W. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J Psychiatr Res. 2015;60:56–64.
    1. Dinoff A., Herrmann N., Swardfager W., Liu C.S., Sherman C., Chan S. The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PLoS One. 2016;11
    1. Dinoff A., Herrmann N., Swardfager W., Lanctot K.L. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis. Eur J Neurosci. 2017;46:1635–1646.
    1. Feter N., Alt R., Dias M.G., Rombaldi A.J. How do different physical exercise parameters modulate brain-derived neurotrophic factor in healthy and non-healthy adults? A systematic review, meta-analysis and meta-regression. Sci Sports. 2019;34:293–304.
    1. Dinoff A., Herrmann N., Swardfager W., Gallagher D., Lanctot K.L. The effect of exercise on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF) in major depressive disorder: a meta-analysis. J Psychiatr Res. 2018;105:123–131.
    1. Kurebayashi Y., Otaki J. Does physical exercise increase brain-derived neurotrophic factor in major depressive disorder? A meta-analysis. Psychiatr Danub. 2018;30:129–135.
    1. Mackay C.P., Kuys S.S., Brauer S.G. The effect of aerobic exercise on brain-derived neurotrophic factor in people with neurological disorders: a systematic review and meta-analysis. Neural Plast. 2017;2017
    1. Hirsch M.A., van Wegen E.E.H., Newman M.A., Heyn P.C. Exercise-induced increase in brain-derived neurotrophic factor in human Parkinson's disease: a systematic review and meta-analysis. Transl Neurodegener. 2018;7:7.
    1. Enette L., Vogel T., Fanon J.L., Lang P.O. Effect of interval and continuous aerobic training on basal serum and plasma brain-derived neurotrophic factor values in seniors: a systematic review of intervention studies. Rejuvenation Res. 2017;20:473–483.
    1. Gold S.M., Schulz K.H., Hartmann S., Mladek M., Lang U.E., Hellweg R. Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol. 2003;138:99–105.
    1. Schulz K.H., Gold S.M., Witte J., Bartsch K., Lang U.E., Hellweg R. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci. 2004;225:11–18.
    1. Rokling-Andersen M.H., Reseland J.E., Veierod M.B., Anderssen S.A., Jacobs D.R., Jr, Urdal P. Effects of long-term exercise and diet intervention on plasma adipokine concentrations. Am J Clin Nutr. 2007;86:1293–1301.
    1. Bonini M., Fioretti D., Sargentini V., Del Giacco S., Rinaldi M., Tranquilli C. Increased nerve growth factor serum levels in top athletes. Clin J Sport Med. 2013;23:228–231.
    1. Bansi J., Bloch W., Gamper U., Kesselring J. Training in MS: influence of two different endurance training protocols (aquatic versus overland) on cytokine and neurotrophin concentrations during three week randomized controlled trial. Mult Scler. 2013;19:613–621.
    1. Kim Y.I. The impact of exercise training on basal BDNF in athletic adolescents. J Phys Ther Sci. 2016;28:3066–3069.
    1. Azali Alamadari K., Choobineh S. Integrated effects of aerobic training on metabolic risk factors, circulatory neurotrophins, testosterone and cortisol in midlife males with metabolic syndrome. Med Sport. 2016;69:228–239.
    1. Cho S.Y., So W.Y., Roh H.T. Effects of aerobic exercise training and cranial electrotherapy stimulation on the stress-related hormone, the neurotrophic factor, and mood states in obese middle-aged women: a pilot clinical trial. Salud Mental. 2016;39:249–256.
    1. Roh H.T., So W.Y. The effects of aerobic exercise training on oxidant-antioxidant balance, neurotrophic factor levels, and blood-brain barrier function in obese and non-obese men. J Sport Health Sci. 2017;6:447–453.
    1. Roh H.T., Cho S.Y., Yoon H.G., So W.Y. Effect of exercise intensity on neurotrophic factors and blood-brain barrier permeability induced by oxidative-nitrosative stress in male college students. Int J Sport Nutr Exerc Metab. 2017;27:239–246.
    1. Mokhtarzade M., Motl R., Negaresh R., Zimmer P., Khodadoost M., Baker J.S. Exercise-induced changes in neurotrophic factors and markers of blood-brain barrier permeability are moderated by weight status in multiple sclerosis. Neuropeptides. 2018;70:93–100.
    1. Moradi H., Sohrabi M., Taheri H., Khodashenas E., Movahedi A. The effects of different combinations of perceptual-motor exercises, music, and vitamin D supplementation on the nerve growth factor in children with high-functioning autism. Complement Ther Clin Pract. 2018;31:139–145.
    1. Domínguez-Sanchez M.A., Bustos-Cruz R.H., Velasco-Orjuela G.P., Quintero A.P., Tordecilla-Sanders A., Correa-Bautista J.E. Acute effects of high intensity, resistance, or combined protocol on the increase of level of neurotrophic factors in physically inactive overweight adults: the Brainfit Study. Front Physiol. 2018;9:741.
    1. Pareja-Galeano H., Alis R., Sanchis-Gomar F., Cabo H., Cortell-Ballester J., Gomez-Cabrera M.C. Methodological considerations to determine the effect of exercise on brain-derived neurotrophic factor levels. Clin Biochem. 2015;48:162–166.
    1. Schiffer T., Schulte S., Sperlich B., Achtzehn S., Fricke H., Struder H.K. Lactate infusion at rest increases BDNF blood concentration in humans. Neurosci Lett. 2011;488:234–237.
    1. Kimhy D., Vakhrusheva J., Bartels M.N., Armstrong H.F., Ballon J.S., Khan S. The impact of aerobic exercise on brain-derived neurotrophic factor and neurocognition in individuals with schizophrenia: a single-blind, randomized clinical trial. Schizophr Bull. 2015;41:859–868.
    1. Heisz J.J., Clark I.B., Bonin K., Paolucci E.M., Michalsk Bi, Becker S. The effects of physical exercise and cognitive training on memory and neurotrophic factors. J Cogn Neurosci. 2017;29:1895–1907.
    1. Leckie R.L., Oberlin L.E., Voss M.W., Prakash R.S., Szabo-Reed A., Chaddock-Heyman L. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front Hum Neurosci. 2014;8:985.
    1. Hakansson K., Ledreux A., Daffner K., Terjestam Y., Bergman P., Carlsson R. BDNF responses in healthy older persons to 35 minutes of physical exercise, cognitive training, and mindfulness: associations with working memory function. J Alzheimers Dis. 2017;55:645–657.
    1. Hill T., Polk J.D. BDNF, endurance activity, and mechanisms underlying the evolution of hominin brains. Am J Phys Anthropol. 2019;168(Suppl. 67):S47–62.
    1. Park S.A., Lee A.Y., Park H.G., Lee W.L. Benefits of gardening activities for cognitive function according to measurement of brain nerve growth factor levels. Int J Environ Res Public Health. 2019;16 pii: E760.
    1. Jiang L., Zhang H., Wang C., Ming F., Shi X., Yang M. Serum level of brain-derived neurotrophic factor in Parkinson's disease: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2019;88:168–174.
    1. Qin X.Y., Cao C., Cawley N.X., Liu T.T., Yuan J., Loh Y.P. Decreased peripheral brain-derived neurotrophic factor levels in Alzheimer's disease: a meta-analysis study (N=7277) Mol Psychiatry. 2017;22:312–320.

Source: PubMed

3
Subscribe