All about running: Synaptic plasticity, growth factors and adult hippocampal neurogenesis

Current Topics in Behavioral Neurosciences

Volumn 15, Issue , 2012, Pages 189-210

  Vivar, Carmen ^a   Potter, Michelle C ^a   van Praag, Henriette ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

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

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; DULOXETINE; ENDOCANNABINOID; FIBROBLAST GROWTH FACTOR 2; GROWTH FACTOR; NERVE GROWTH FACTOR; OPIATE RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; SOMATOMEDIN C; TRANSCRIPTION FACTOR; VASCULOTROPIN; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID;

AGE; ANTIDEPRESSANT ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER; BRAIN BLOOD VESSEL; DENDRITIC SPINE; DENTATE GYRUS; DEPRESSION; ENDURANCE TRAINING; GABAERGIC TRANSMISSION; GLUTAMATERGIC SYNAPSE; HIPPOCAMPUS; HUMAN; LEARNING; LONG TERM POTENTIATION; MEMORY; MONOAMINERGIC SYSTEM; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEUROTRANSMISSION; NONHUMAN; PHYSICAL ACTIVITY; PRIORITY JOURNAL; RUNNING; SKELETAL MUSCLE; ANIMAL; COGNITION; METABOLISM; PHYSIOLOGY; REVIEW; SYNAPTIC TRANSMISSION;

ANIMALS; COGNITION; HIPPOCAMPUS; NEUROGENESIS; NEURONAL PLASTICITY; RUNNING; SYNAPTIC TRANSMISSION;

EID: 84891701025     PISSN: 18663370     EISSN: 18663389     Source Type: Book Series    
DOI: 10.1007/7854_2012_220     Document Type: Article

References (167)

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: 2896-2903
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): 43-48
3. Adlard PA et al (2005) Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. J Neurosci 25: 4217-4221
4. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3): 319-335
5. Altschuler EL (2006) Strenuous, intensive, long-term exercise does not prevent or delay the onset of Huntington's disease. Med Hypotheses 67: 1429-1430
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: 633-638
7. Bakker A, Kirwan CB, Miller M, Stark CE (2008) Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 5870(319): 1640-1642
8. Baruch DE, Swain RA, Helmstetter FJ (2004) Effects of exercise on Pavlovian fear conditioning. Behav Neurosci 118: 1123-1127
9. BearMF, AbrahamWC(1996)Long-term depression in hippocampus. AnnuRevNeurosci 19: 437-462
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): e13993
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: 536-542
12. Berchtold NC, Castello N, Cotman CW (2010) Exercise and time-dependent benefits to learning and memory. Neuroscience 167: 588-597
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: 853-861
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: 15570-15575
15. Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22: 123-131
16. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31-39
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: 2042-2046
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): 1323-1329
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: 2926-2933
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: 827-835
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: 208-213
22. Chaouloff F (1989) Physical exercise and brain monoamines: a review. Acta Physiol Scand 137: 1-13
23. Chevrel G, Hohlfeld R, Sendtner M (2006) The role of neurotrophins in muscle under physiological and pathological conditions. Muscle Nerve 33(4): 462-476
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: 937-950
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): 210-213
26. Cotman CW, Berchtold NC (2002) Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25: 295-301
27. Cotman CW, Berchtold NC, Christie LA (2007) Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30: 464-472
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: 2367-2372
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: 823-833
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: 39-47
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: 845-851
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: 8233-8238
33. Erickson CA, Barnes CA (2003) The neurobiology of memory changes in normal aging. Exp Gerontol 38: 61-69
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: 84-92
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: 2803-2812
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: 50
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: 125-129
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: 321-331
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: 71-79
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): 728-734
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: 123-133
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: 13368-13383
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): 421-454
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: 559-566
45. Gilbert PE, Kesner RP, Lee I (2001) Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus 6(11): 626-633
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): 808-814
47. Gómez-Pinilla F, Dao L, So V (1997) Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res 764: 1-8
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): 2187-2195
49. Gómez-Pinilla F (2008) Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci J 9(7): 568-758
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: 4549-4552
51. Greenough WT, West RW, DeVoogd TJ (1978) Subsynaptic plate perforations: changes with age and experience in the rat. Science 202(4372): 1096-1098
52. GreenoughWT, McDonald JW, Parnisari RM, Camel JE (1986) Environmental conditionsmodulate degeneration and new dendrite growth in cerebellum of senescent rats. Brain Res 380: 136-143
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): 988-1001
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: 973-980
55. Hanson ND, Owens MJ, Nemeroff CB (2011) Depression, antidepressants, and neurogenesis: a critical reappraisal. Neuropsychopharmacology 36: 2589-2602
56. Hardie DG (2004) AMP-activated protein kinase: a key system mediating metabolic responses to exercise. Med Sci Sports Exerc 36: 28-34
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: 353-371
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): 844-851
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: 513-523
60. Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 9: 58-65
61. Hopkins ME, Bucci DJ (2010) Interpreting the effects of exercise on fear conditioning: the influence of time of day. Behav Neurosci 124: 868-872
62. Huff NC, Rudy JW (2004) The amygdala modulates hippocampus-dependent context memory formation and stores cue-shock associations. Behav Neurosci 118(1): 53-62
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: 573-585
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 SciUSA99: 11946-11950
65. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386: 493-495
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: 939-942
67. Kesner RP (2007) Behavioral functions of the CA3 subregion of the hippocampus. Learn Mem 14(11): 771-781
68. Kitamura T, Mishina M, Sugiyama H (2003) Enhancement of neurogenesis by running wheel exercises is suppressed inmice lackingNMDAreceptor epsilon 1 subunit. Neurosci Res 47: 55-63
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: 605-609
70. Kobilo T, Yuan C, van Praag H (2011b) Endurance factors improve hippocampal neurogenesis and spatial memory in mice. Learn Mem 18: 103-107
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: 24-33
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: 8856-8860
73. Korte M, Griesbeck O, Gravel C, Carroll P, Staiger V, Thoenen H, Bonhoeffer T (1996) Virusmediated gene transfer into hippocampal CA1 region restores long-term potentiation in brainderived neurotrophic factor mutant mice. Proc Natl Acad Sci U S A 93: 12547-12552
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: 1637-1640
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: 1505-1513
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: 455-563
77. Krum JM, Mani N, Rosenstein JM (2002) Angiogenic and astroglial responses to vascular endothelial growth factor administration in adult rat brain. Neuroscience 110: 589-604
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: 2027-2033
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: 580-586
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: 34
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: 206-216
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): 267-277
83. Lautenschlager NT, Cox K, Cyarto EV (2012) The influence of exercise on brain aging and dementia. Biochim Biophys Acta 1822(3): 474-481
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: 763-767
85. Leutgeb JK, Leutgeb S, Moser MB, Moser EI (2007) Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315(5814): 961-966
86. Leutgeb S, Leutgeb JK (2007) Pattern separation, pattern completion, and new neuronal codes within a continuous CA3 map. Learn Mem 14(11): 745-757
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: 399-412
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: 603-613
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): 140-147
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: 81-89
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: 9833-9838
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: 48-55
93. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20: 9104-9110
94. Maren S (2001) Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci 24: 897-931
95. Maren S (2008) Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats. Eur J Neurosci 28(8): 1661-1666
96. Marlatt MW, Lucassen PJ, van Praag H (2010) Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice. Brain Res 1341: 93-99
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
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): 94-99
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: 364-369
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: 1107-1116
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: 767
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): 835-847
104. Nägerl UV, Eberhorn N, Cambridge SB, Bonhoeffer T (2004) Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 44: 759-767
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: 405-415
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: 14632-14637
107. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373: 109
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: 49-56
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): 124-132
110. Nichol K et al (2009) Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice. Alzheimers Dement 5: 287-294
111. O'Callaghan RM, Ohle R, KellyAM(2007) The effects offorced exercise on hippocampal plasticity in the rat: Acomparison of LTP, spatial-and non-spatial learning. Behav Brain Res 176: 362-366
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: 1019-10129
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: 11410-11415
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: 479-494
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: 569-584
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: 1137-1145
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: 5638-5643
119. Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106(2): 274-285
120. Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2: 24-32
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: RRN1201
122. Radley JJ, Jacobs BL (2002) 5-HT1A receptor antagonist administration decreases cell proliferation in the dentate gyrus. Brain Res 955: 264-267
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: 1765-1779
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: 63-71
125. Redila VA, Christie BR (2006) Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus. Neurosci 137: 1299-1307
126. Reinhardt RR, Bondy CA (1994) Insulin-like growth factors cross the blood-brain barrier. Endocrinology 135: 1753-1761
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): e2935
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): 707-717
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: 466-470
130. Sakuma K, Yamaguchi A (2011) The recent understanding of the neurotrophin's role in skeletal muscle adaptation. J Biomed Biotechnol 2011: 201696
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: 805-809
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: 348-356
133. Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429: 184-187
134. Schmidt B, Marrone DF, Markus EJ (2012) Disambiguating the similar: the dentate gyrus and pattern separation. Behav Brain Res 226(1): 56-65
135. Schwarz L, Kindermann W (1992) Changes in beta-endorphin levels in response to aerobic and anaerobic exercise. Sports Med 13: 25-36
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: 380-384
137. Stranahan AM, Khalil D, Gould E (2007) Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus 17: 1017-1022
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: 394-403
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: 80-92
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: 1628-1634
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. ProcNatlAcad SciUSA107(17): 7963-7968
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: 25-31
143. van Dellen A, Blakemore C, Deacon R, York D, Hannan AJ (2000) Delaying the onset of Huntington's in mice. Nature 404: 721-722
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: 34
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: 928-936
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): 324-334
147. van Praag H (2008) Neurogenesis and exercise: past and future directions. Neuromolecular 10: 128-140
148. van Praag H (2009) Exercise and the brain: something to chew on. Trends Neurosci 32: 283-290
149. van Praag H, Kempermann G, Gage FH (1999a) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2: 266-270
150. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1(3): 191-198
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: 13427-13431
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: 5869-5878
153. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415: 1030-1034
154. van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25: 8680-8685
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: 1201-1208
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: 283-295
157. Vaynman S, Ying Z, Gómez-Pinilla F (2004a) Exercise induces BDNF and synapsin I to specific hippocampal subfields. J Neurosci Res 76: 356-362
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: 2580-2590
159. Wang S, Scott BW, Martin JM (2000) Heterogeneous properties of dentate granule neurons in the adult rat. J Neurobiol 42: 248-257
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): e294
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: 1605-17
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): 5484-5491
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: 9329-9338
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: 1585-1594
165. Yamada K, Nabeshima T (2003) Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci 91: 267-270
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: 5874-5879
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: 3-11