The Journal of Physiological Sciences

, Volume 67, Issue 6, pp 681–687 | Cite as

BDNF levels are increased in peripheral blood of middle-aged amateur runners with no changes on histone H4 acetylation levels

  • Fernanda Peres da Silveira
  • Carla Basso
  • Wagner Raupp
  • Morgana Dalpiaz
  • Karine Bertoldi
  • Ionara Rodrigues Siqueira
  • Pedro Dal Lago
  • Maristela Padilha de Souza
  • Viviane Rostirola Elsner
Original Paper


Our aim was to compare the basal levels of plasma brain-derived neurotrophic factor (BDNF) and global histone H4 acetylation in peripheral blood mononuclear cells (PBMCs) of healthy amateur runners (EXE group) with sedentary individuals (SED group) as well as to investigate the acute effect of a running race on these markers in the EXE group. Five days before the race, all participants were submitted to a basal blood collection. On the race day, two blood samples were collected in the EXE group before the running started and immediately at the end. In the basal period, a significant increase of plasma BDNF levels in the EXE individuals when compared to the SED group (p = 0.036) was demonstrated, while no difference in global histone H4 acetylation levels was observed. These parameters were unaltered in the EXE group after the race. The increased levels of BDNF might be linked to healthy middle-aged runners’ phenotype.


Exercise Epigenetic Neurotrophins Adult men Plasma Peripheral blood mononuclear cells (PBMCs) 



This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq/Brazil; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/Brazil and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2(1):24–32CrossRefPubMedGoogle Scholar
  2. 2.
    Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22(3):123–131CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 37(12):1553–1561CrossRefPubMedGoogle Scholar
  4. 4.
    Schuch FB, da Silveira LE, de Zeni TC, da Silva DP, Wollenhaupt-Aguiar B, Ferrari P, Reischak-Oliveira A, Kapczinski F (2015) Effects of a single bout of maximal aerobic exercise on BDNF in bipolar disorder: a gender-based response. Psychiatry Res 229(1–2):57–62CrossRefPubMedGoogle Scholar
  5. 5.
    Erickson KI, Miller DL, Roecklein KA (2012) The aging hippocampus: interactions between exercise, depression, and BDNF. Neuroscientist 18(1):82–97CrossRefPubMedGoogle Scholar
  6. 6.
    Zoladz JA, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, Duda K (2008) Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol 7:119–132Google Scholar
  7. 7.
    Zoladz JA, Pilc A (2010) The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. J Physiol Pharmacol 61(5):533–541PubMedGoogle Scholar
  8. 8.
    Jeon YK, Ha CH (2015) Expression of brain-derived neurotrophic factor, IGF-1 and cortisol elicited by regular aerobic exercise in adolescents. J Phys Ther Sci 27(3):737–741CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Babaei P, Azali Alamdari K, Soltani Tehrani B, Damirchi A (2013) Effect of six weeks of endurance exercise and following detraining on serum brain-derived neurotrophic factor and memory performance in middle-aged males with metabolic syndrome. J Sports Med Phys Fit 53(4):437–743Google Scholar
  10. 10.
    Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, Adser H, Jakobsen AH, Pilegaard H, Nielsen HB, Secher NH (2010) Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol 298(2):R372–R377CrossRefPubMedGoogle Scholar
  11. 11.
    Rosa JP, de Souza AA, de Lima GH, Rodrigues DF, de Aquino Lemos V, da Silva Alves E, Tufik S, de Mello MT (2015) Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study. Front Psychol 6:648CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Elsner VR, Lovatel GA, Bertoldi K, Vanzella C, Santos FM, Spindler C, de Almeida EF, Nardin P, Siqueira IR (2011) Effect of different exercise protocols on histone acetyltransferases and histone deacetylases activities in rat hippocampus. Neurosci 192:580–587CrossRefGoogle Scholar
  13. 13.
    Elsner VR, Lovatel GA, Moyses F, Bertoldi K, Spindler C, Cechinel LR, Muotri AR, Siqueira IR (2013) Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study. Exp Gerontol 48(2):136–139CrossRefPubMedGoogle Scholar
  14. 14.
    Gomez-Pinilla F, Zhuang Y, Feng J, Ying Z, Fan G (2011) Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur J Neurosci 33(3):383–390CrossRefPubMedGoogle Scholar
  15. 15.
    Spindler C, Cechinel LR, Basso C, Moyses F, Bertoldi K, Roesler R, Lovatel GA, Rostirola Elsner V, Siqueira IR (2014) Treadmill exercise alters histone acetyltransferases and histone deacetylases activities in frontal cortices from Wistar rats. Cell Mol Neurobiol 34(8):1097–1101CrossRefPubMedGoogle Scholar
  16. 16.
    Tsankova N, Renthal W, Kumar A, Nestler EJ (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8(5):355–367CrossRefPubMedGoogle Scholar
  17. 17.
    Sultan FA, Day JJ (2011) Epigenetic mechanisms in memory and synaptic function. Epigenomics 3(2):157–181CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705CrossRefPubMedGoogle Scholar
  19. 19.
    Zhang Y, Hashimoto S, Fujii C, Hida S, Ito K, Matsumura T, Sakaizawa T, Morikawa M, Masuki S, Nose H, Higuchi K, Nakajima K, Taniguchi S (2015) NFkappaB2 gene as a novel candidate that epigenetically responds to interval walking training. Int J Sports Med 36(9):769–775CrossRefPubMedGoogle Scholar
  20. 20.
    Zimmer P, Baumann FT, Bloch W, Schenk A, Koliamitra C, Jensen P, Mierau A, Hulsdunker T, Reinart N, Hallek M, Elter T (2014) Impact of exercise on pro inflammatory cytokine levels and epigenetic modulations of tumor-competitive lymphocytes in non-Hodgkin-lymphoma patients-randomized controlled trial. Eur J Haematol 93(6):527–532CrossRefPubMedGoogle Scholar
  21. 21.
    Zimmer P, Bloch W, Schenk A, Zopf EM, Hildebrandt U, Streckmann F, Beulertz J, Koliamitra C, Schollmayer F, Baumann F (2015) Exercise-induced natural killer cell activation is driven by epigenetic modifications. Int J Sports Med 36(6):510–515CrossRefPubMedGoogle Scholar
  22. 22.
    Dorneles GP, da Silva IRV, Korb A, Bertoldi K, Siqueira IR, Elsner VR, Romão PRT, Peres A (2016) High-intensity interval exercise enhances the global HDAC activity in PBMC and anti-inflammatory cytokines of overweight-obese subjects. Obes Med 2:25–30CrossRefGoogle Scholar
  23. 23.
    Lovatel GA, Elsner VR, Bertoldi K, Vanzella C, Moysés Fdos S, Vizuete A, Spindler C, Cechinel LR, Netto CA, Muotri AR, Siqueira IR (2013) Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiol Learn Mem 101:94–102CrossRefPubMedGoogle Scholar
  24. 24.
    Barrichello T, Generoso JS, Simões LR, Faller CJ, Ceretta RA, Petronilho F, Lopes-Borges J, Valvassori SS, Quevedo J (2015) Sodium butyrate prevents memory impairment by re-establishing BDNF and GDNF expression in experimental pneumococcal meningitis. Mol Neurobiol 52(1):734–740CrossRefGoogle Scholar
  25. 25.
    Wu X, Chen PS, Dallas S, Wilson B, Block ML, Wang CC, Kinyamu H, Lu N, Gao X, Leng Y, Chuang DM, Zhang W, Lu RB, Hong JS (2008) Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int J Neuropsychopharmacol 11(8):1123–1134CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Zhu X, Li Q, Chang R, Yang D, Song Z, Guo Q, Huang C (2014) Curcumin alleviates neuropathic pain by inhibiting 300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model. PLoS One 9(3):e91303CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Chandwani S, Keilani S, Ortiz-Virumbrales M, Morant A, Bezdecny S, Ehrlich ME (2013) Induction of DARPP-32 by brain-derived neurotrophic factor in striatal neurons in vitro is modified by histone deacetylase inhibitors and Nab2. PLoS One 8(10):e76842CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Uchida H, Matsushita Y, Ueda H (2013) Epigenetic regulation of BDNF expression in the primary sensory neurons after peripheral nerve injury: implications in the development of neuropathic pain. Neurosci 14(240):147–154CrossRefGoogle Scholar
  29. 29.
    Jia M, Liu WX, Sun HL, Chang YQ, Yang JJ, Ji MH, Yang JJ, Feng CZ (2015) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, attenuates postoperative cognitive dysfunction in aging mice. Front Mol Neurosci 23(8):52Google Scholar
  30. 30.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMedGoogle Scholar
  31. 31.
    Noble EE, Billington CJ, Kotz CM, Wang C (2011) The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol 300(5):R1053–R1069CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Mattson MP (2012) Evolutionary aspects of human exercise–born to run purposefully. Ageing Res Rev 11(3):347–352CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Abel JL, Rissman EF (2013) Running-induced epigenetic and gene expression changes in the adolescent brain. Int J Dev Neurosci 31(6):382–390CrossRefPubMedGoogle Scholar
  34. 34.
    Petersen SE, van Mier H, Fiez JA, Raichle ME (1998) The effects of practice on the functional anatomy of task performance. Proc Natl Acad Sci USA 95(3):853–860CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ferris LT, Williams JS, Shen CL (2007) The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc 39(4):728–734CrossRefPubMedGoogle Scholar
  36. 36.
    Gilder M, Ramsbottom R, Currie J, Sheridan B, Nevill AM (2014) Effect of fat free mass on serum and plasma BDNF concentrations during exercise and recovery in healthy young men. Neurosci Lett 7(560):137–141CrossRefGoogle Scholar
  37. 37.
    Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H (2009) Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94(10):1062–1069CrossRefPubMedGoogle Scholar
  38. 38.
    Robson-Ansley PJ, Saini A, Toms C, Ansley L, Walshe IH, Nimmo MA, Curtin JA (2014) Dynamic changes in DNA methylation status in peripheral blood mononuclear cells following an acute bout of exercise: potential impact of exercise-induced elevations in interleukin-6 concentration. J Biol Regul Homeost Agents 28(3):407–417PubMedGoogle Scholar
  39. 39.
    McGee SL, Fairlie E, Garnham AP, Hargreaves M (2009) Exercise-induced histone modifications in human skeletal muscle. J Physiol 587(Pt 24):5951–5958CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Barres R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O’Gorman DJ, Zierath JR (2012) Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 15(3):405–411CrossRefPubMedGoogle Scholar
  41. 41.
    Denham J, O’Brien BJ, Marques FZ, Charchar FJ (2015) Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise. J Appl Physiol 118(4):475–488CrossRefPubMedGoogle Scholar
  42. 42.
    Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH, Nilsson E, Tornberg A, Dekker Nitert M, Eriksson KF, Jones HA, Groop L, Ling C (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 6:e1003572CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  • Fernanda Peres da Silveira
    • 1
  • Carla Basso
    • 2
  • Wagner Raupp
    • 2
  • Morgana Dalpiaz
    • 1
  • Karine Bertoldi
    • 2
  • Ionara Rodrigues Siqueira
    • 2
  • Pedro Dal Lago
    • 3
  • Maristela Padilha de Souza
    • 1
  • Viviane Rostirola Elsner
    • 1
  1. 1.Programa de Pós Graduação em Biociências e Reabilitação do Centro Universitário Metodista do IPAPorto AlegreBrazil
  2. 2.Programa de Pós Graduação Ciências Biológicas: FisiologiaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Programa de Pós Graduação em Ciências da ReabilitaçãoUniversidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil

Personalised recommendations