Skip to main content

Physical exercise, neuroplasticity, spatial learning and memory

Abstract

There has long been discussion regarding the positive effects of physical exercise on brain activity. However, physical exercise has only recently begun to receive the attention of the scientific community, with major interest in its effects on the cognitive functions, spatial learning and memory, as a non-drug method of maintaining brain health and treating neurodegenerative and/or psychiatric conditions. In humans, several studies have shown the beneficial effects of aerobic and resistance exercises in adult and geriatric populations. More recently, studies employing animal models have attempted to elucidate the mechanisms underlying neuroplasticity related to physical exercise-induced spatial learning and memory improvement, even under neurodegenerative conditions. In an attempt to clarify these issues, the present review aims to discuss the role of physical exercise in the improvement of spatial learning and memory and the cellular and molecular mechanisms involved in neuroplasticity.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    American College of Sports Medicine (1990) American College of Sports Medicine position stand. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness in healthy adults. Med Sci Sports Exerc 22:265–274

    Google Scholar 

  2. 2.

    Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A (2007) Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 39:1423–1434

    PubMed  Article  Google Scholar 

  3. 3.

    Meeusen R (2005) Exercise and the brain: insight in new therapeutic modalities. Ann Transplant 10:49–51

    PubMed  Google Scholar 

  4. 4.

    Cotman CW, Berchtold NC (2007) Physical activity and the maintenance of cognition: learning from animal models. Alzheimers Dement 3:S30–S37

    PubMed  Article  Google Scholar 

  5. 5.

    Chaddock L, Hillman CH, Buck SM, Cohen NJ (2011) Aerobic fitness and executive control of relational memory in preadolescent children. Med Sci Sports Exerc 43:344–349

    PubMed  Article  Google Scholar 

  6. 6.

    Chaddock L, Erickson KI, Prakash RS, Kim JS, Voss MW, Vanpatter M, Pontifex MB, Raine LB, Konkel A, Hillman CH, Cohen NJ, Kramer AF (2010) A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. Brain Res 1358:172–183

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  7. 7.

    Herting MM, Nagel BJ (2012) Aerobic fitness relates to learning on a virtual Morris water task and hippocampal volume in adolescents. Behav Brain Res 233:517–525

    PubMed Central  PubMed  Article  Google Scholar 

  8. 8.

    Cassilhas RC, Viana VA, Grassmann V, Santos RT, Santos RF, Tufik S, Mello MT (2007) The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 39:1401–1407

    PubMed  Article  Google Scholar 

  9. 9.

    Cassilhas RC, Lee KS, Fernandes J, Oliveira MG, Tufik S, Meeusen R, de Mello MT (2012) Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience 202:309–317

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Leuner B, Gould E (2010) Structural plasticity and hippocampal function. Annu Rev Psychol 61:111–113

    PubMed Central  PubMed  Article  Google Scholar 

  11. 11.

    Knaepen K, Goekint M, Heyman EM, Meeusen R (2010) Neuroplasticity—exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med 40:765–801

    PubMed  Article  Google Scholar 

  12. 12.

    Johnston MV (2009) Plasticity in the developing brain: implications for rehabilitation. Dev Disabil Res Rev 15:94–101

    PubMed  Article  Google Scholar 

  13. 13.

    Johnston MV (2004) Clinical disorders of brain plasticity. Brain Dev 26:73–80

    PubMed  Article  Google Scholar 

  14. 14.

    Leahey TH, Harris RJ (2001) Neurophysiology of learning and cognition. In: Leahey TH, Harris RJ (eds) Learning and cognition. Prentice-Hall, New Jersey, pp 353–377

    Google Scholar 

  15. 15.

    Lent R (2004) Cem Bilhões de Neurônios, 2nd edn. Atheneu, São Paulo

    Google Scholar 

  16. 16.

    Voss MW, Vivar C, Kramer AF, van Praag H (2013) Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci 17:525–544

    PubMed Central  PubMed  Article  Google Scholar 

  17. 17.

    van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270

    PubMed  Article  Google Scholar 

  18. 18.

    van Praag H (2008) Neurogenesis and exercise: past and future directions. Neuromolecular Med 10:128–140

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Marr D (1971) Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci 262:23–81

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ (2010) Running enhances spatial pattern separation in mice. Proc Natl Acad Sci 107:2367–2372

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  21. 21.

    Dery N, Pilgrim M, Gibala M, Gillen J, Wojtowicz JM, Macqueen G, Becker S (2013) Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression. Front Neurosci 7:66

    PubMed Central  PubMed  Article  Google Scholar 

  22. 22.

    Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS, White SM, Wojcicki TR, McAuley E, Kramer AF (2009) Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus 19:1030–1039

    PubMed Central  PubMed  Article  Google Scholar 

  23. 23.

    Stranahan AM, Khalil D, Gould E (2006) Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci 9:526–533

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  24. 24.

    van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci 96:13427–13431

    PubMed Central  PubMed  Article  Google Scholar 

  25. 25.

    van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25:8680–8685

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  26. 26.

    Stranahan AM, Khalil D, Gould E (2007) Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus 17:1017–1022

    PubMed Central  PubMed  Article  Google Scholar 

  27. 27.

    Eadie BD, Redila VA, Christie BR (2005) Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. J Comp Neurol 486:39–47

    PubMed  Article  Google Scholar 

  28. 28.

    Meeusen R, De Meirleir K (1995) Exercise and brain neurotransmission. Sports Med 20:160–188

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Vaynman S, Gomez-Pinilla F (2005) License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil Neural Repair 19:283–295

    PubMed  Article  Google Scholar 

  30. 30.

    Vaynman S, Ying Z, Gomez-Pinilla F (2004) Exercise induces BDNF and synapsin I to specific hippocampal subfields. J Neurosci Res 76:356–362

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F (2006) Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience 140:823–833

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Trejo JL, Carro E, Torres-Aleman I (2001) Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 21:1628–1634

    CAS  PubMed  Google Scholar 

  33. 33.

    Schinder AF, Berninger B, Poo M (2000) Postsynaptic target specificity of neurotrophin-induced presynaptic potentiation. Neuron 25:151–163

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Schinder AF, Poo M (2000) The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci 23:639–645

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Tsao D, Thomsen HK, Chou J, Stratton J, Hagen M, Loo C, Garcia C, Sloane DL, Rosenthal A, Lin JC (2008) TrkB agonists ameliorate obesity and associated metabolic conditions in mice. Endocrinology 149:1038–1048

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Nakagawa T, Ono-Kishino M, Sugaru E, Yamanaka M, Taiji M, Noguchi H (2002) Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice. Diabetes Metab Res Rev 18:185–191

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Hubka P (2006) Neural network plasticity, BDNF and behavioral interventions in Alzheimer’s disease. Bratisl Lek Listy 107:395–401

    CAS  PubMed  Google Scholar 

  38. 38.

    Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M (2010) Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 11:763–773

    PubMed  Article  Google Scholar 

  39. 39.

    Castren E, Rantamaki T (2010) The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev Neurobiol 70:289–297

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Cunha AB, Frey BN, Andreazza AC, Goi JD, Rosa AR, Goncalves CA, Santin A, Kapczinski F (2006) Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett 398:215–219

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Minichiello L (2009) TrkB signalling pathways in LTP and learning. Nat Rev Neurosci 10:850–860

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Pang PT, Teng HK, Zaitsev E, Woo NT, Sakata K, Zhen S, Teng KK, Yung WH, Hempstead BL, Lu B (2004) Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306:487–491

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Friedman WJ (2000) Neurotrophins induce death of hippocampal neurons via the p75 receptor. J Neurosci 20:6340–6346

    CAS  PubMed  Google Scholar 

  44. 44.

    Neeper SA, Gomez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373:109

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Bloor CM (2005) Angiogenesis during exercise and training. Angiogenesis 8:263–271

    PubMed  Article  Google Scholar 

  46. 46.

    Gomez-Pinilla F, Dao L, So V (1997) Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res 764:1–8

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    da Gomes S, Unsain N, Masco DH, Toscano-Silva M, de Amorim HA, Silva Araujo BH, Simoes PS, Graca Naffah-Mazzacoratti M, Mortara RA, Scorza FA, Cavalheiro EA, Arida RM (2010) Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats. Hippocampus 22:347–358

    Article  Google Scholar 

  48. 48.

    Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW (1996) Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 726:49–56

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Vaynman S, Ying Z, Gomez-Pinilla F (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20:2580–2590

    PubMed  Article  Google Scholar 

  50. 50.

    Radak Z, Toldy A, Szabo Z, Siamilis S, Nyakas C, Silye G, Jakus J, Goto S (2006) The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochem Int 49:387–392

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Griffin EW, Bechara RG, Birch AM, Kelly AM (2009) Exercise enhances hippocampal-dependent learning in the rat: evidence for a BDNF-related mechanism. Hippocampus 19:973–980

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Vaynman SS, Ying Z, Yin D, Gomez-Pinilla F (2006) Exercise differentially regulates synaptic proteins associated to the function of BDNF. Brain Res 1070:124–130

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    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 59(Suppl 7):119–132

    PubMed  Google Scholar 

  54. 54.

    Zoladz JA, Pilc A (2010) The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. J Physiol Pharmacol 61:533–541

    CAS  PubMed  Google Scholar 

  55. 55.

    Cohen P (2006) Overview of the IGF-I system. Horm Res 65(Suppl 1):3–8

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Daughaday WH, Hall K, Salmon WD Jr, Van den Brande JL, Van Wyk JJ (1987) On the nomenclature of the somatomedins and insulin-like growth factors. J Clin Endocrinol Metab 65:1075–1076

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Werther GA, Abate M, Hogg A, Cheesman H, Oldfield B, Hards D, Hudson P, Power B, Freed K, Herington AC (1990) Localization of insulin-like growth factor-I mRNA in rat brain by in situ hybridization—relationship to IGF-I receptors. Mol Endocrinol 4:773–778

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Bondy CA, Werner H, Roberts CT Jr, LeRoith D (1990) Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. Mol Endocrinol 4:1386–1398

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Nishijima T, Piriz J, Duflot S, Fernandez AM, Gaitan G, Gomez-Pinedo U, Verdugo JM, Leroy F, Soya H, Nunez A, Torres-Aleman I (2010) Neuronal activity drives localized blood-brain-barrier transport of serum insulin-like growth factor-I into the CNS. Neuron 67:834–846

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Russo VC, Gluckman PD, Feldman EL, Werther GA (2005) The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 26:916–943

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Annenkov A (2009) The insulin-like growth factor (IGF) receptor type 1 (IGF1R) as an essential component of the signalling network regulating neurogenesis. Mol Neurobiol 40:195–215

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Ye P, D’Ercole AJ (2006) Insulin-like growth factor actions during development of neural stem cells and progenitors in the central nervous system. J Neurosci Res 83:1–6

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Philippou A, Halapas A, Maridaki M, Koutsilieris M (2007) Type I insulin-like growth factor receptor signaling in skeletal muscle regeneration and hypertrophy. J Musculoskelet Neuronal Interact 7:208–218

    CAS  PubMed  Google Scholar 

  64. 64.

    Landret GA (1999) Growth factors. In: Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds) Basic neurochemistry: molecular, cellular and medical aspects. Lippincott Williams & Wilkins, Philadelphia, pp 383–398

    Google Scholar 

  65. 65.

    Aleman A, Verhaar HJ, de Haan EH, De Vries WR, Samson MM, Drent ML, Van der Veen EA, Koppeschaar HP (1999) Insulin-like growth factor-I and cognitive function in healthy older men. J Clin Endocrinol Metab 84:471–475

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Dik MG, Pluijm SM, Jonker C, Deeg DJ, Lomecky MZ, Lips P (2003) Insulin-like growth factor I (IGF-I) and cognitive decline in older persons. Neurobiol Aging 24:573–581

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Kalmijn S, Janssen JA, Pols HA, Lamberts SW, Breteler MM (2000) A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly. J Clin Endocrinol Metab 85:4551–4555

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Morley JE, Kaiser F, Raum WJ, Perry HM III, Flood JF, Jensen J, Silver AJ, Roberts E (1997) Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci 94:7537–7542

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  69. 69.

    Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte MR, Rizzo MR, Carella C, Varricchio M (1997) Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab 82:2204–2209

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Rollero A, Murialdo G, Fonzi S, Garrone S, Gianelli MV, Gazzerro E, Barreca A, Polleri A (1998) Relationship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects. Neuropsychobiology 38:73–79

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Arwert LI, Deijen JB, Drent ML (2005) The relation between insulin-like growth factor I levels and cognition in healthy elderly: a meta-analysis. Growth Horm IGF Res 15:416–422

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    O’Callaghan RM, Griffin EW, Kelly AM (2009) Long-term treadmill exposure protects against age-related neurodegenerative change in the rat hippocampus. Hippocampus 19:1019–1029

    PubMed  Article  CAS  Google Scholar 

  73. 73.

    Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124:71–79

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Bear MF, Abraham WC (1996) Long-term depression in hippocampus. Annu Rev Neurosci 19:437–462

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Vasuta C, Caunt C, James R, Samadi S, Schibuk E, Kannangara T, Titterness AK, Christie BR (2007) Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus. Hippocampus 17:1201–1208

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Morgenstern NA, Lombardi G, Schinder AF (2008) Newborn granule cells in the ageing dentate gyrus. J Physiol 586:3751–3757

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  77. 77.

    Cirillo J, Lavender AP, Ridding MC, Semmler JG (2009) Motor cortex plasticity induced by paired associative stimulation is enhanced in physically active individuals. J Physiol 587:5831–5842

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  78. 78.

    Fathi D, Ueki Y, Mima T, Koganemaru S, Nagamine T, Tawfik A, Fukuyama H (2010) Effects of aging on the human motor cortical plasticity studied by paired associative stimulation. Clin Neurophysiol 121:90–93

    PubMed  Article  Google Scholar 

  79. 79.

    Carro E, Trejo JL, Busiguina S, Torres-Aleman I (2001) Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 21:5678–5684

    CAS  PubMed  Google Scholar 

  80. 80.

    Carro E, Nunez A, Busiguina S, Torres-Aleman I (2000) Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci 20:2926–2933

    CAS  PubMed  Google Scholar 

  81. 81.

    Gomez-Pinilla F, Ying Z, Opazo P, Roy RR, Edgerton VR (2001) Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur J Neurosci 13:1078–1084

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Ang ET, Dawe GS, Wong PT, Moochhala S, Ng YK (2006) Alterations in spatial learning and memory after forced exercise. Brain Res 1113:186–193

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Correia PR, Pansani A, Machado F, Andrade M, Silva AC, Scorza FA, Cavalheiro EA, Arida RM (2010) Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels. Clinics (Sao Paulo) 65:1123–1126

    Article  Google Scholar 

  84. 84.

    Goekint M, De Pauw K, Roelands B, Njemini R, Bautmans I, Mets T, Meeusen R (2010) Strength training does not influence serum brain-derived neurotrophic factor. Eur J Appl Physiol 110:285–293

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Vale RG, de Oliveira RD, Pernambuco CS, de Meneses YP, Novaes JS, de Andrade AF (2009) Effects of muscle strength and aerobic training on basal serum levels of IGF-1 and cortisol in elderly women. Arch Gerontol Geriatr 49:343–347

    CAS  PubMed  Article  Google Scholar 

  86. 86.

    Cassilhas RC, Antunes HK, Tufik S, de Mello MT (2010) Mood, anxiety, and serum IGF-1 in elderly men given 24 weeks of high resistance exercise. Percept Mot Skills 110:265–276

    PubMed  Article  Google Scholar 

  87. 87.

    Borst SE, De Hoyos DV, Garzarella L, Vincent K, Pollock BH, Lowenthal DT, Pollock ML (2001) Effects of resistance training on insulin-like growth factor-I and IGF binding proteins. Med Sci Sports Exerc 33:648–653

    CAS  PubMed  Article  Google Scholar 

  88. 88.

    Arikawa AY, Kurzer MS, Thomas W, Schmitz KH (2010) No effect of exercise on insulin-like growth factor-I, insulin, and glucose in young women participating in a 16-week randomized controlled trial. Cancer Epidemiol Biomark Prev 19:2987–2990

    CAS  Article  Google Scholar 

  89. 89.

    McTiernan A, Sorensen B, Yasui Y, Tworoger SS, Ulrich CM, Irwin ML, Rudolph RE, Stanczyk FZ, Schwartz RS, Potter JD (2005) No effect of exercise on insulin-like growth factor 1 and insulin-like growth factor binding protein 3 in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol Biomark Prev 14:1020–1021

    CAS  Article  Google Scholar 

  90. 90.

    Ari Z, Kutlu N, Uyanik BS, Taneli F, Buyukyazi G, Tavli T (2004) Serum testosterone, growth hormone, and insulin-like growth factor-1 levels, mental reaction time, and maximal aerobic exercise in sedentary and long-term physically trained elderly males. Int J Neurosci 114:623–637

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Carro E, Torres-Aleman I (2006) Serum insulin-like growth factor I in brain function. Keio J Med 55:59–63

    CAS  PubMed  Article  Google Scholar 

  92. 92.

    Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–335

    CAS  PubMed  Article  Google Scholar 

  93. 93.

    Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660

    CAS  PubMed  Article  Google Scholar 

  94. 94.

    Trejo JL, Llorens-Martin MV, Torres-Aleman I (2008) The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci 37:402–411

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Speisman RB, Kumar A, Rani A, Foster TC, Ormerod BK (2013) Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats. Brain Behav Immun 28:25–43

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  96. 96.

    Moon HY, Kim SH, Yang YR, Song P, Yu HS, Park HG, Hwang O, Lee-Kwon W, Seo JK, Hwang D, Choi JH, Bucala R, Ryu SH, Kim YS, Suh PG (2012) Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise. Proc Natl Acad Sci 109:13094–13099

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  97. 97.

    Vukovic J, Colditz MJ, Blackmore DG, Ruitenberg MJ, Bartlett PF (2012) Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J Neurosci 32:6435–6443

    CAS  PubMed  Article  Google Scholar 

  98. 98.

    Hill MN, Titterness AK, Morrish AC, Carrier EJ, Lee TT, Gil-Mohapel J, Gorzalka BB, Hillard CJ, Christie BR (2010) Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus 20:513–523

    PubMed Central  CAS  PubMed  Google Scholar 

  99. 99.

    Klempin F, Kempermann G (2007) Adult hippocampal neurogenesis and aging. Eur Arch Psychiatry Clin Neurosci 257:271–280

    PubMed  Article  Google Scholar 

  100. 100.

    Marlatt MW, Potter MC, Lucassen PJ, van Praag H (2012) Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Dev Neurobiol 72:943–952

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  101. 101.

    Llorens-Martin MV, Rueda N, Tejeda GS, Florez J, Trejo JL, Martinez-Cue C (2010) Effects of voluntary physical exercise on adult hippocampal neurogenesis and behavior of Ts65Dn mice, a model of down syndrome. Neuroscience 171:1228–1240

    CAS  PubMed  Article  Google Scholar 

  102. 102.

    Rodriguez JJ, Jones VC, Tabuchi M, Allan SM, Knight EM, LaFerla FM, Oddo S, Verkhratsky A (2008) Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One 3:e2935

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  103. 103.

    Heyn P, Abreu BC, Ottenbacher KJ (2004) The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis. Arch Phys Med Rehabil 85:1694–1704

    PubMed  Article  Google Scholar 

  104. 104.

    Heyn PC, Johnson KE, Kramer AF (2008) Endurance and strength training outcomes on cognitively impaired and cognitively intact older adults: a meta-analysis. J Nutr Health Aging 12:401–409

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  105. 105.

    Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, Bussey TJ (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  106. 106.

    Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ (2011) Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol 22:536–542

    CAS  PubMed  Article  Google Scholar 

  107. 107.

    Oomen CA, Bekinschtein P, Kent BA, Saksida LM, Bussey TJ (2014) Adult hippocampal neurogenesis and its role in cognition. Wiley Interdiscip Rev Cogn Sci 5:573–587

    PubMed Central  PubMed  Article  Google Scholar 

  108. 108.

    van Praag H (2009) Exercise and the brain: something to chew on. Trends Neurosci 32:283–290

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  109. 109.

    Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, Konda S, Engberg K, Lauterbur PC, Greenough WT (2003) Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience 117:1037–1046

    CAS  PubMed  Article  Google Scholar 

  110. 110.

    Ding YH, Li J, Zhou Y, Rafols JA, Clark JC, Ding Y (2006) Cerebral angiogenesis and expression of angiogenic factors in aging rats after exercise. Curr Neurovasc Res 3:15–23

    CAS  PubMed  Article  Google Scholar 

  111. 111.

    Burdette JH, Laurienti PJ, Espeland MA, Morgan A, Telesford Q, Vechlekar CD, Hayasaka S, Jennings JM, Katula JA, Kraft RA, Rejeski WJ (2010) Using network science to evaluate exercise-associated brain changes in older adults. Front Aging Neurosci 2:23

    PubMed Central  PubMed  Google Scholar 

  112. 112.

    Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA (2007) An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci 104:5638–5643

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  113. 113.

    Bullitt E, Rahman FN, Smith JK, Kim E, Zeng D, Katz LM, Marks BL (2009) The effect of exercise on the cerebral vasculature of healthy aged subjects as visualized by MR angiography. AJNR Am J Neuroradiol 30:1857–1863

    CAS  PubMed  Article  Google Scholar 

  114. 114.

    Vaynman S, Ying Z, Gomez-Pinilla F (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20:2580–2590

    PubMed  Article  Google Scholar 

Download references

Acknowledgments

We apologize for not reviewing numerous pertinent articles because of space limitations. The authors would like to thanks the São Paulo Research Foundation (FAPESP) (post-doctoral grant Dr. Ricardo C. Cassilhas – number 2013/05018-5). For the academic and financial support, the authors are grateful to Department of Physical Education – Universidade Federal dos Vales do Jequitinhonha e Mucuri (UVFJM), School of Physical Education, Physiotherapy and Occupational Therapy (EEFFTO) – Universidade Federal de Minas Gerais (UFMG), Department of Psychobiology – Universidade Federal de São Paulo (UNIFESP) and National Council for Scientific and Technological Development (CNPq) (Grant number 478229/2013-5 – chamada Universal).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Marco Túlio de Mello.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cassilhas, R.C., Tufik, S. & de Mello, M.T. Physical exercise, neuroplasticity, spatial learning and memory. Cell. Mol. Life Sci. 73, 975–983 (2016). https://doi.org/10.1007/s00018-015-2102-0

Download citation

Keywords

  • Aerobic exercise
  • Resistance exercise
  • Neuroplasticity
  • Brain
  • Cognition
  • Memory