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All About Running: Synaptic Plasticity, Growth Factors and Adult Hippocampal Neurogenesis

  • Carmen Vivar
  • Michelle C. Potter
  • Henriette van PraagEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 15)

Abstract

Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF).

Keywords

Adult neurogenesis Dentate gyrus Running Learning and memory Neurotrophic factors Synaptic plasticity Endurance factors 

Notes

Acknowledgments

This work was supported by the National Institute on Aging, Intramural Research Program.

References

  1. Aberg MA, Aberg ND, Hedbäcker H, Oscarsson J, Eriksson PS (2000) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 20:2896–2903PubMedGoogle Scholar
  2. Adlard PA, Perreau VM, Engesser-Cesar C, Cotman CW (2004) The timecourse of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise. Neurosci Lett 363(1):43–48PubMedGoogle Scholar
  3. Adlard PA et al (2005) Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci 25:4217–4221PubMedGoogle Scholar
  4. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3):319–335PubMedGoogle Scholar
  5. Altschuler EL (2006) Strenuous, intensive, long-term exercise does not prevent or delay the onset of Huntington’s disease. Med Hypotheses 67:1429–1430PubMedGoogle Scholar
  6. Babyak M, Blumenthal JA, Herman S, Khatri P, Doraiswamy M, Moore K, Craighead WE, Baldewicz TT, Krishnan KR (2000) Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med 62:633–638PubMedGoogle Scholar
  7. Bakker A, Kirwan CB, Miller M, Stark CE (2008) Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 5870(319):1640–1642Google Scholar
  8. Baruch DE, Swain RA, Helmstetter FJ (2004) Effects of exercise on Pavlovian fear conditioning. Behav Neurosci 118:1123–1127PubMedGoogle Scholar
  9. Bear MF, Abraham WC (1996) Long-term depression in hippocampus. Annu Rev Neurosci 19:437–462PubMedGoogle Scholar
  10. Beauquis J, Roig P, De Nicola AF, Saravia F (2010) Short-term environmental enrichment enhances adult neurogenesis, vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice. PLoS One 5(11):e13993PubMedGoogle Scholar
  11. 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 22:536–542PubMedGoogle Scholar
  12. Berchtold NC, Castello N, Cotman CW (2010) Exercise and time-dependent benefits to learning and memory. Neuroscience 167:588–597PubMedGoogle Scholar
  13. Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW (2005) Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 133:853–861PubMedGoogle Scholar
  14. Bergami M, Rimondini R, Santi S, Blum R, Götz M, Canossa M (2008) Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior. Proc Natl Acad Sci U S A. 105:15570–15575PubMedGoogle Scholar
  15. Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22:123–131PubMedGoogle Scholar
  16. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39PubMedGoogle Scholar
  17. Brown J, Cooper-Kuhn CM, Kempermann G, Van Praag H, Winkler J, Gage FH, Kuhn HG (2003) Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci 17:2042–2046PubMedGoogle Scholar
  18. Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA (2012) Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology 78(17):1323–1329PubMedGoogle Scholar
  19. Carro E, Nuñez A, Busiguina S, Torres-Aleman I (2000) Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci 20:2926–2933PubMedGoogle Scholar
  20. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, During MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36:827–835PubMedGoogle Scholar
  21. Chae CH, Kim HT (2009) Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochem Int 55:208–213PubMedGoogle Scholar
  22. Chaouloff F (1989) Physical exercise and brain monoamines: a review. Acta Physiol Scand 137:1–13PubMedGoogle Scholar
  23. Chevrel G, Hohlfeld R, Sendtner M (2006) The role of neurotrophins in muscle under physiological and pathological conditions. Muscle Nerve 33(4):462–476PubMedGoogle Scholar
  24. Clark PJ, Brzezinska WJ, Puchalski EK, Krone DA, Rhodes JS (2009) Functional analysis of neurovascular adaptations to exercise in the dentate gyrus of young adult mice associated with cognitive gain. Hippocampus 19:937–950PubMedGoogle Scholar
  25. 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(5937):210–213PubMedGoogle Scholar
  26. Cotman CW, Berchtold NC (2002) Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25:295–301PubMedGoogle Scholar
  27. Cotman CW, Berchtold NC, Christie LA (2007) Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30:464–472PubMedGoogle Scholar
  28. Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ (2010) Running enhances spatial pattern separation in mice. Proc Natl Acad Sci U S A 107:2367–2372PubMedGoogle Scholar
  29. 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 140:823–833PubMedGoogle Scholar
  30. 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 486:39–47PubMedGoogle Scholar
  31. Ehninger D, Kempermann G (2003) Regional effects of wheel running and environmental enrichment on cell genesis and microglia proliferation in the adult murine neocortex. Cereb Cortex 13:845–851PubMedGoogle Scholar
  32. Encinas JM, Vaahtokari A, Enikolopov G (2006) Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci U S A 103:8233–8238PubMedGoogle Scholar
  33. Erickson CA, Barnes CA (2003) The neurobiology of memory changes in normal aging. Exp Gerontol 38:61–69PubMedGoogle Scholar
  34. Ernst C, Olson AK, Pinel JP, Lam RW, Christie BR (2006) Antidepressant effects of exercise: evidence for an adult-neurogenesis hypothesis? J Psychiatr Neurosci 31:84–92Google Scholar
  35. Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, Palmer TD (2003) VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 18:2803–2812PubMedGoogle Scholar
  36. Fabel K, Wolf SA, Ehninger D, Babu H, Leal-Galicia P, Kempermann G (2009) Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Front Neurosci 3:50PubMedGoogle Scholar
  37. Fahey B, Barlow S, Day JS, O’Mara SM (2008) Interferon-alpha-induced deficits in novel object recognition are rescued by chronic exercise. Physiol Behav 95:125–129PubMedGoogle Scholar
  38. Falls WA, Fox JH, MacAulay CM (2010) Voluntary exercise improves both learning and consolidation of cued conditioned fear in C57 mice. Behav Brain Res 207:321–331PubMedGoogle Scholar
  39. 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. Neurosci 124:71–79Google Scholar
  40. 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):728–734PubMedGoogle Scholar
  41. Fordyce DE, Farrar RP (1991) Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning. Behav Brain Res 46:123–133PubMedGoogle Scholar
  42. Galvão RP, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Brain-derived neurotrophic factor signaling does not stimulate subventricular zone neurogenesis in adult mice and rats. J Neurosci 28:13368–13383PubMedGoogle Scholar
  43. García-Mesa Y, López-Ramos JC, Giménez-Llort L, Revilla S, Guerra R, Gruart A, Laferla FM, Cristòfol R, Delgado-García JM, Sanfeliu C (2011) Physical exercise protects against Alzheimer’s disease in 3xTg-AD mice. J Alzheimers Dis 24(3):421–454PubMedGoogle Scholar
  44. Ge S, Yang C, Hsu K, Ming G, Song H (2007) A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54:559–566PubMedGoogle Scholar
  45. Gilbert PE, Kesner RP, Lee I (2001) Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus 6(11):626–633Google Scholar
  46. Gold AE, Kesner RP (2005) The role of the CA3 subregion of the dorsal hippocampus in spatial pattern completion in the rat. Hippocampus 15(6):808–814PubMedGoogle Scholar
  47. Gómez-Pinilla F, Dao L, So V (1997) Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res 764:1–8PubMedGoogle Scholar
  48. Gómez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR (2002) Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 88(5):2187–2195PubMedGoogle Scholar
  49. Gómez-Pinilla F (2008) Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci J 9(7):568–758Google Scholar
  50. Greenough WT, Hwang HM, Gorman C (1985) Evidence for active synapse formation or altered postsynaptic metabolism in visual cortex of rats reared in complex environments. Proc Natl Acad Sci U S A 82:4549–4552PubMedGoogle Scholar
  51. Greenough WT, West RW, DeVoogd TJ (1978) Subsynaptic plate perforations: changes with age and experience in the rat. Science 202(4372):1096–1098PubMedGoogle Scholar
  52. Greenough WT, McDonald JW, Parnisari RM, Camel JE (1986) Environmental conditionsmodulate degeneration and new dendrite growth in cerebellum of senescent rats. Brain Res 380:136–143PubMedGoogle Scholar
  53. Greenwood BN, Strong PV, Foley TE, Fleshner M (2009) A behavioral analysis of the impact of voluntary physical activity on hippocampus-dependent contextual conditioning. Hippocampus 19(10):988–1001PubMedGoogle Scholar
  54. Griffin EW, Bechara RG, Birch AM, Kelly AM (2009) Exercise enhances hippocampal-dependent learning in the rat: evidence for a BDNF-related mechanism. Hippocampus 19:973–980PubMedGoogle Scholar
  55. Hanson ND, Owens MJ, Nemeroff CB (2011) Depression, antidepressants, and neurogenesis: a critical reappraisal. Neuropsychopharmacology 36:2589–2602PubMedGoogle Scholar
  56. Hardie DG (2004) AMP-activated protein kinase: a key system mediating metabolic responses to exercise. Med Sci Sports Exerc 36:28–34PubMedGoogle Scholar
  57. Hattiangady B, Rao MS, Shetty GA, Shetty AK (2005) Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus. Exp Neurol 195:353–371PubMedGoogle Scholar
  58. Heyman E, Gamelin FX, Goekint M, Piscitelli F, Roelands B, Leclair E, Di Marzo V, Meeusen R (2012) Intense exercise increases circulating endocannabinoid and BDNF levels in humans–possible implications for reward and depression. Psychoneuroendocrinology 37(6):844–851PubMedGoogle Scholar
  59. 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 20:513–523PubMedGoogle Scholar
  60. Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 9:58–65PubMedGoogle Scholar
  61. Hopkins ME, Bucci DJ (2010) Interpreting the effects of exercise on fear conditioning: the influence of time of day. Behav Neurosci 124:868–872PubMedGoogle Scholar
  62. Huff NC, Rudy JW (2004) The amygdala modulates hippocampus-dependent context memory formation and stores cue-shock associations. Behav Neurosci 118(1):53–62PubMedGoogle Scholar
  63. Ip EY, Giza CC, Griesbach GS, Hovda DA (2002) Effects of enriched environment and fluid percussion injury on dendritic arborization within the cerebral cortex of the developing rat. J Neurotrauma 19:573–585PubMedGoogle Scholar
  64. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 99:11946–11950PubMedGoogle Scholar
  65. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495PubMedGoogle Scholar
  66. Kempermann G, Brandon EP, Gage FH (1998) Environmental stimulation of 129/SvJ mice causes increased cell proliferation and neurogenesis in the adult dentate gyrus. Curr Biol 8:939–942PubMedGoogle Scholar
  67. Kesner RP (2007) Behavioral functions of the CA3 subregion of the hippocampus. Learn Mem 14(11):771–781PubMedGoogle Scholar
  68. Kitamura T, Mishina M, Sugiyama H (2003) Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor epsilon 1 subunit. Neurosci Res 47:55–63PubMedGoogle Scholar
  69. Kobilo T, Liu QR, Gandhi K, Mughal M, Shaham Y, van Praag H (2011a) Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learn Mem 18:605–609PubMedGoogle Scholar
  70. Kobilo T, Yuan C, van Praag H (2011b) Endurance factors improve hippocampal neurogenesis and spatial memory in mice. Learn Mem 18:103–107PubMedGoogle Scholar
  71. Kohl Z, Kandasamy M, Winner B, Aigner R, Gross C, Couillard-Despres S, Bogdahn U, Aigner L, Winkler J (2007) Physical activity fails to rescue hippocampal neurogenesis deficits in the R6/2 mouse model of Huntington’s disease. Brain Res 1155:24–33PubMedGoogle Scholar
  72. Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A 92:8856–8860PubMedGoogle Scholar
  73. Korte M, Griesbeck O, Gravel C, Carroll P, Staiger V, Thoenen H, Bonhoeffer T (1996) Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice. Proc Natl Acad Sci U S A 93:12547–12552PubMedGoogle Scholar
  74. Kosinski CM, Schlangen C, Gellerich FN, Gizatullina Z, Deschauer M, Schiefer J, Young AB, Landwehrmeyer GB, Toyka KV, Sellhaus B, Lindenberg KS (2007) Myopathy as a first symptom of Huntington’s disease in a Marathon runner. Mov Disord 22:1637–1640PubMedGoogle Scholar
  75. Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G (2006) Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 27:1505–1513PubMedGoogle Scholar
  76. Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–563PubMedGoogle Scholar
  77. Krum JM, Mani N, Rosenstein JM (2002) Angiogenic and astroglial responses to vascular endothelial growth factor administration in adult rat brain. Neuroscience 110:589–604PubMedGoogle Scholar
  78. Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033PubMedGoogle Scholar
  79. Kuipers SD, Bramham CR (2006) Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr Opin Drug Discov Devel 9:580–586PubMedGoogle Scholar
  80. Lafenêtre P, Leske O, Ma-Högemeie Z, Haghikia A, Bichler Z, Wahle P, Heumann R (2010) Exercise can rescue recognition memory impairment in a model with reduced adult hippocampal neurogenesis. Front Behav Neurosci 3:34PubMedGoogle Scholar
  81. Lambert TJ, Fernandez SM, Frick KM (2005) Different types of environmental enrichment have discrepant effects on spatial memory and synaptophysin levels in female mice. Neurobiol Learn Mem 83:206–216PubMedGoogle Scholar
  82. Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR; International Huntington’s Disease Collaborative Group (2004) A new model for prediction of the age of onset and penetrance for Huntington’s disease based on CAG length. Clin Genet 65(4):267–277Google Scholar
  83. Lautenschlager NT, Cox K, Cyarto EV (2012) The influence of exercise on brain aging and dementia. Biochim Biophys Acta 1822(3):474–481Google Scholar
  84. Lawlor DA, Hopker SW (2001) The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ 322:763–767PubMedGoogle Scholar
  85. Leutgeb JK, Leutgeb S, Moser MB, Moser EI (2007) Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315(5814):961–966PubMedGoogle Scholar
  86. Leutgeb S, Leutgeb JK (2007) Pattern separation, pattern completion, and new neuronal codes within a continuous CA3 map. Learn Mem 14(11):745–757PubMedGoogle Scholar
  87. Li Y, Luikart BW, Birnbaum S, Chen J, Kwon CH, Kernie SG, Bassel-Duby R, Parada LF (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59:399–412PubMedGoogle Scholar
  88. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613PubMedGoogle Scholar
  89. Lin TW, Chen SJ, Huang TY, Chang CY, Chuang JI, Wu FS, Kuo YM, Jen CJ (2012) Different types of exercise induce differential effects on neuronal adaptations and memory performance. Neurobiol Learn Mem 97(1):140–147PubMedGoogle Scholar
  90. Liu YF, Chen HI, Yu L, Kuo YM, Wu FS, Chuang JI, Liao PC, Jen CJ (2008) Upregulation of hippocampal TrkB and synaptotagmin is involved in treadmill exercise-enhanced aversive memory in mice. Neurobiol Learn Mem 90:81–89PubMedGoogle Scholar
  91. Lopez–Lopez C, LeRoith D, Torres-Aleman I (2004) Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proc Natl Acad Sci U S A 101:9833–9838PubMedGoogle Scholar
  92. Lou SJ, Liu JY, Chang H, Chen PJ (2008) Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats. Brain Res 1210:48–55PubMedGoogle Scholar
  93. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110PubMedGoogle Scholar
  94. Maren S (2001) Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci 24:897–931PubMedGoogle Scholar
  95. Maren S (2008) Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats. Eur J Neurosci 28(8):1661–1666PubMedGoogle Scholar
  96. Marlatt MW, Lucassen PJ, van Praag H (2010) Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice. Brain Res 1341:93–99PubMedGoogle Scholar
  97. 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/6 J mice. Dev Neurobiol doi: 10.1002/dneu.22009 Google Scholar
  98. McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist JK, Lowell BB, Fanselow MS, Wilson MA, Tonegawa S (2007) Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317(5834):94–99PubMedGoogle Scholar
  99. Mello PB, Benetti F, Cammarota M, Izquierdo I (2009) Physical exercise can reverse the deficit in fear memory induced by maternal deprivation. Neurobiol Learn Mem 92:364–369PubMedGoogle Scholar
  100. Molteni R, Ying Z, Gómez-Pinilla F (2002) Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci 16:1107–1116PubMedGoogle Scholar
  101. Morton AJ, Skillings E, Bussey TJ, Saksida LM (2006) Measuring cognitive deficits in disabled mice using an automated interactive touchscreen system. Nat Methods 3:767PubMedGoogle Scholar
  102. Mustroph ML, Chen, S, Desai SC, Cay EB, DeYoung EK, Rhodes JS. (2012) Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6 J mice, Neuroscience, doi: http://dx.doi.org/10.1016/j.neuroscience.2012.06.007
  103. Myers CE, Gluck MA (1994) Context, conditioning, and hippocampal rerepresentation in animal learning. Behav Neurosci 108(5):835–847PubMedGoogle Scholar
  104. Nägerl UV, Eberhorn N, Cambridge SB, Bonhoeffer T (2004) Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 44:759–767PubMedGoogle Scholar
  105. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell 134:405–415PubMedGoogle Scholar
  106. Naylor AS, Bull C, Nilsson MK, Zhu C, Björk-Eriksson T, Eriksson PS, Blomgren K, Kuhn HG (2008) Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A 105:14632–14637PubMedGoogle Scholar
  107. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373:109PubMedGoogle Scholar
  108. Neeper SA, Gómez-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 726:49–56PubMedGoogle Scholar
  109. Nichol KE, Parachikova AI, Cotman CW (2007) Three weeks of running wheel exposure improves cognitive performance in the aged Tg2576 mouse. Behav Brain Res 184(2):124–132PubMedGoogle Scholar
  110. Nichol K et al (2009) Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice. Alzheimers Dement 5:287–294PubMedGoogle Scholar
  111. O’Callaghan RM, Ohle R, Kelly AM (2007) The effects of forced exercise on hippocampal plasticity in the rat: A comparison of LTP, spatial- and non-spatial learning. Behav Brain Res 176:362–366PubMedGoogle Scholar
  112. O’Callaghan RM, Griffin EW, Kelly AM (2009) Long-term treadmill exposure protects against age-related neurodegenerative change in the rat hippocampus. Hippocampus 19:1019–10129PubMedGoogle Scholar
  113. Ogunshola OO, Antic A, Donoghue MJ, Fan SY, Kim H, Stewart WB, Madri JA, Ment LR (2002) Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. J Biol Chem 277:11410–11415PubMedGoogle Scholar
  114. Ota KT, Duman RS (2012) Environmental and pharmacological modulations of cellular plasticity: role in the pathophysiology and treatment of depression. Neurobiol Dis http://dx.doi.org/10.1016/j.bbr.2011.03.031
  115. Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494PubMedGoogle Scholar
  116. Pang TY, Stam NC, Nithianantharajah J, Howard ML, Hannan AJ (2006) Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in Huntington’s disease transgenic mice. Neuroscience 141:569–584PubMedGoogle Scholar
  117. Patterson SL, Abel T, Deuel TA, Martin KC, Rose JC, Kandel ER (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16:1137–1145PubMedGoogle Scholar
  118. 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 U S A 104:5638–5643PubMedGoogle Scholar
  119. Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106(2):274–285PubMedGoogle Scholar
  120. Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2:24–32PubMedGoogle Scholar
  121. Potter MC, Yuan C, Ottenritter C, Mughal M, van Praag H (2010) Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease. PLoS Curr. 2:RRN1201Google Scholar
  122. Radley JJ, Jacobs BL (2002) 5-HT1A receptor antagonist administration decreases cell proliferation in the dentate gyrus. Brain Res 955:264–267PubMedGoogle Scholar
  123. Rai KS, Hattiangady B, Shetty AK (2007) Enhanced production and dendritic growth of new dentate granule cells in the middle-aged hippocampus following intracerebroventricular FGF-2 infusions. Eur J Neurosci 26:1765–1779PubMedGoogle Scholar
  124. Real CC, Ferreira AF, Hernandes MS, Britto LR, Pires RS (2010) Exercise-induced plasticity of AMPA-type glutamate receptor subunits in the rat brain. Brain Res 1363:63–71PubMedGoogle Scholar
  125. Redila VA, Christie BR (2006) Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus. Neurosci 137:1299–1307Google Scholar
  126. Reinhardt RR, Bondy CA (1994) Insulin-like growth factors cross the blood-brain barrier. Endocrinology 135:1753–1761PubMedGoogle Scholar
  127. Rodríguez 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 13;3(8):e2935Google Scholar
  128. Rodríguez JJ, Noristani HN, Olabarria M, Fletcher J, Somerville TD, Yeh CY, Verkhratsky A (2011) Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimer’s disease. Curr Alzheimer Res 8(7):707–717PubMedGoogle Scholar
  129. Sahay A, Scobie KN, Hill AS, O’Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R (2011) Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472:466–470PubMedGoogle Scholar
  130. Sakuma K, Yamaguchi A (2011) The recent understanding of the neurotrophin’s role in skeletal muscle adaptation. J Biomed Biotechnol 2011:201696PubMedGoogle Scholar
  131. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809PubMedGoogle Scholar
  132. Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S (2005) Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 192:348–356PubMedGoogle Scholar
  133. Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429:184–187PubMedGoogle Scholar
  134. Schmidt B, Marrone DF, Markus EJ (2012) Disambiguating the similar: the dentate gyrus and pattern separation. Behav Brain Res 226(1):56–65PubMedGoogle Scholar
  135. Schwarz L, Kindermann W (1992) Changes in beta-endorphin levels in response to aerobic and anaerobic exercise. Sports Med 13:25–36PubMedGoogle Scholar
  136. Sforzo GA, Seeger TF, Pert CB, Pert A, Dotson CO (1986) In vivo opioid receptor occupation in the rat brain following exercise. Med Sci Sports Exerc 18:380–384PubMedGoogle Scholar
  137. Stranahan AM, Khalil D, Gould E (2007) Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus 17:1017–1022PubMedGoogle Scholar
  138. Suwa M, Nakano H, Radak Z, Kumagai S (2011) Short-term adenosine monophosphate-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle. Metabolism 60:394–403PubMedGoogle Scholar
  139. Taliaz D, Stall N, Dar DE, Zangen A (2010) Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry 15:80–92PubMedGoogle Scholar
  140. 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 21:1628–1634PubMedGoogle Scholar
  141. Tronel S, Fabre A, Charrier V, Oliet SH, Gage FH, Abrous DN (2010) Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons. Proc Natl Acad Sci U S A 107(17):7963–7968PubMedGoogle Scholar
  142. Titterness AK, Wiebe E, Kwasnica A, Keyes G, Christie BR (2011) Voluntary exercise does not enhance long-term potentiation in the adolescent female dentate gyrus. Neuroscience 183:25–31PubMedGoogle Scholar
  143. van Dellen A, Blakemore C, Deacon R, York D, Hannan AJ (2000) Delaying the onset of Huntington’s in mice. Nature 404:721–722PubMedGoogle Scholar
  144. van Dellen A, Cordery PM, Spires TL, Blakemore C, Hannan AJ (2008) Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington’s disease. BMC Neurosci 9:34PubMedGoogle Scholar
  145. Van der Borght K, Kóbor-Nyakas DE, Klauke K, Eggen BJ, Nyakas C, Van der Zee EA, Meerlo P (2009) Physical exercise leads to rapid adaptations in hippocampal vasculature: temporal dynamics and relationship to cell proliferation and neurogenesis. Hippocampus 19:928–936PubMedGoogle Scholar
  146. Van der Borght K, Havekes R, Bos T, Eggen BJ, Van der Zee EA (2007) Exercise improves memory acquisition and retrieval in the Y-maze task: relationship with hippocampal neurogenesis. Behav Neurosci 121(2):324–334PubMedGoogle Scholar
  147. van Praag H (2008) Neurogenesis and exercise: past and future directions. Neuromolecular 10:128–140Google Scholar
  148. van Praag H (2009) Exercise and the brain: something to chew on. Trends Neurosci 32:283–290PubMedGoogle Scholar
  149. van Praag H, Kempermann G, Gage FH (1999a) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270PubMedGoogle Scholar
  150. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1(3):191–198PubMedGoogle Scholar
  151. van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999b) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96:13427–13431PubMedGoogle Scholar
  152. van Praag H, Lucero MJ, Yeo GW, Stecker K, Heivand N, Zhao C, Yip E, Afanador M, Schroeter H, Hammerstone J, Gage FH (2007) Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 27:5869–5878PubMedGoogle Scholar
  153. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034PubMedGoogle Scholar
  154. van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25:8680–8685PubMedGoogle Scholar
  155. 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 17:1201–1208PubMedGoogle Scholar
  156. 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 19:283–295PubMedGoogle Scholar
  157. Vaynman S, Ying Z, Gómez-Pinilla F (2004a) Exercise induces BDNF and synapsin I to specific hippocampal subfields. J Neurosci Res 76:356–362PubMedGoogle Scholar
  158. Vaynman S, Ying Z, Gomez-Pinilla F (2004b) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20:2580–2590PubMedGoogle Scholar
  159. Wang S, Scott BW, Martin JM (2000) Heterogeneous properties of dentate granule neurons in the adult rat. J Neurobiol 42:248–257PubMedGoogle Scholar
  160. Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, Bayuga-Ocampo CR, Ham J, Kang H, Evans RM (2004) Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2(10):e294PubMedGoogle Scholar
  161. Werner S, Unsicker K, von Bohlen und Halbach O. (2011) Fibroblast growth factor-2 deficiency causes defects in adult hippocampal neurogenesis, which are not rescued by exogenous fibroblast growth factor-2. J Neurosci Res. 89:1605–17Google Scholar
  162. Wiltgen BJ, Sanders MJ, Anagnostaras SG, Sage JR, Fanselow MS (2006) Context fear learning in the absence of the hippocampus. J Neurosci 26(20):5484–5491PubMedGoogle Scholar
  163. Wong-Goodrich SJ, Pfau ML, Flores CT, Fraser JA, Williams CL, Jones LW (2010) Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer Res 70:9329–9338PubMedGoogle Scholar
  164. Wu CW, Chang YT, Yu L, Chen HI, Jen CJ, Wu SY, Lo CP, Kuo YM (2008) Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice. J Appl Physiol 105:1585–1594PubMedGoogle Scholar
  165. Yamada K, Nabeshima T (2003) Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci 91:267–270PubMedGoogle Scholar
  166. Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C, Bakowska JC, Breakefield XO, Moskowitz MA (2001) FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci USA 98:5874–5879PubMedGoogle Scholar
  167. Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 26:3–11PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Carmen Vivar
    • 1
  • Michelle C. Potter
    • 1
  • Henriette van Praag
    • 1
    Email author
  1. 1.Neuroplasticity and Behavior Unit, Laboratory of NeurosciencesNIA/NIH Biomedical Research CenterBaltimoreUSA

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