Skip to main content
Log in

Exercise and Brain Health — Implications for Multiple Sclerosis

Part 1 — Neuronal Growth Factors

  • Leading Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

The benefits of regular exercise to promote general health and reduce the risk of hypokinetic diseases associated with sedentary lifestyles are well recognized. Recent studies suggest that exercise may enhance neurobiological processes that promote brain health in aging and disease. A current frontier in the neurodegenerative disorder multiple sclerosis (MS) concerns the role of physical activity for promoting brain health through protective, regenerative and adaptive neural processes. Research on neuromodulation, raises the possibility that regular physical activity may mediate favourable changes in disease factors and symptoms associated with MS, in part through changes in neuroactive proteins. Insulin-like growth factor-I appears to act as a neuroprotective agent and studies indicate that exercise could promote this factor in MS. Neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor likely play roles in neuronal survival and activity-dependent plasticity. Physical activity has also been shown to upregulate hippocampal BDNF, which may play a role in mood states, learning and memory to lessen the decline in cognitive function associated with MS. In addition, exercise may promote anti-oxidant defences and neurotrophic support that could attenuate CNS vulnerability to neuronal degeneration. Exercise exposure (preconditioning) may serve as a mechanism to enhance stress resistance and thereby may support neuronal survival under heightened stress conditions. Considering that axonal loss and cerebral atrophy occur early in the disease, exercise prescription in the acute stage could promote neuroprotection, neuroregeneration and neuroplasticity and reduce long-term disability. This review concludes with a proposed conceptual model to connect these promising links between exercise and brain health.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. White L, Dressendorfer R. Exercise and multiple sclerosis. Sports Med 2004; 34: 1077–100

    Article  PubMed  Google Scholar 

  2. White L, Mc Coy S, Castellano V, et al. Effect of resistance training on risk of coronary artery disease in women with multiple sclerosis. Scand J Clin Lab Invest 2006; 66: 351–5

    Article  PubMed  CAS  Google Scholar 

  3. Kempermann G, van Praag H, Gage FH. Activity—dependent regulation of neuronal plasticity and self repair. Prog Brain Res 2000; 127: 35–48

    Article  PubMed  CAS  Google Scholar 

  4. Kramer A, Hahn S, Cohen N, et al. Ageing, fitness and neurocognitive function. Nature 1999; 4000: 418–9

    Article  CAS  Google Scholar 

  5. Rogers R, Meyer J, Mortel K. After reaching retirement age physical activity sustains cerebral perfusion and cognition. J Am Geriatr Soc 1990; 38: 123–8

    PubMed  CAS  Google Scholar 

  6. Fordyce D, Farrar R. Enhancement of spatial learning in F344 rats by physical activity and related learning—associated alterations in hippocampal and cortical cholinergic functioning. Behav Brain Res 1991; 46: 123–33

    Article  PubMed  CAS  Google Scholar 

  7. van Praag H, Christie BR, Sejnowski TJ, et al. Running enhances neurogenesis, learning, and long—term potentiation in mice. Proc Natl Acad Sci U S A 1999; 96: 13427–31

    Article  PubMed  Google Scholar 

  8. van Praag H, Kempermann G, Gage F. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266–70

    Article  PubMed  Google Scholar 

  9. Smith AD, Zigmond MJ. Can the brain be protected through exercise? Lessons from an animal model of parkinsonism. Exp Neurol 2003; 184: 31–9

    Article  PubMed  CAS  Google Scholar 

  10. Stummer W, Weber K, Tranmer B, et al. Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia. Stroke 1994; 25: 1862–7

    Article  PubMed  CAS  Google Scholar 

  11. Adlard P, Perreau V, Pop V, et al. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci 2005; 25: 4217–22

    Article  PubMed  CAS  Google Scholar 

  12. Lyngberg K, Danneskiold-Samsoe B, Halskov O. The effect of physical training on patients with rheumatoid arthritis: changes in disease activity, muscle strength and aerobic capacity: a clinically controlled minimized cross—over study. Clin Exp Rheumatol 1988; 6: 253–60

    PubMed  CAS  Google Scholar 

  13. Le Page C, Ferry A, Rieu M. Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis. J Appl Physiol 1994; 77: 2341–7

    PubMed  Google Scholar 

  14. Le Page C, Bourdoulous S, Beraud E, et al. Effect of physical exercise on adoptive experimental auto—immune encephalomyelitis in rats. Eur J Appl Physiol Occup Physiol 1996; 73: 130–5

    Article  PubMed  Google Scholar 

  15. Larsen J, Skalicky M, Viidik A. Does long—term physical exercise counteract age—related Purkinje cell loss? A stereological study of rat cerebellum. J Comp Neurol 2000; 428: 213–22

    Article  PubMed  CAS  Google Scholar 

  16. Mattson M. Neuroprotective signaling and the aging brain: take away my food and let me run. Brain Res 2000; 866: 47–53

    Article  Google Scholar 

  17. Neeper S, Gomez-Pinilla F, Choi J, et al. Exercise and brain neurotrophins. Nature 1995; 373: 109

    Article  PubMed  CAS  Google Scholar 

  18. Neeper SA, Gomez-Pinilla F, Choi J, et al. Physical activity increases mRNA for brain—derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 1996; 726: 49–56

    Article  PubMed  CAS  Google Scholar 

  19. Oliff H, Berchtold N, Isackson P, et al. Exercise—induced regulation of brain—derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. Brain Res Mol Brain Res 1998; 61: 147–53

    Article  PubMed  CAS  Google Scholar 

  20. Widenfalk J, Olson L, Thoren P. Deprived of habitual running, rats downregulate BDNF and TrkB messages in the brain. Neurosci Res 1999; 34: 125–32

    Article  PubMed  CAS  Google Scholar 

  21. Ang ET, Wong PTH, Moochhala S, et al. Neuroprotection associated with running: is it a result of increased endogenous neurotrophic factors? Neuroscience 2003; 118: 335–45

    Article  PubMed  CAS  Google Scholar 

  22. Carro E, Trejo J, Nunez A, et al. Brain repair and neuroprotection by serum insulin—like growth factor I. Mol Neurobiol 2003; 27: 153–6

    Article  PubMed  CAS  Google Scholar 

  23. Mattson MP, Maudsley S, Martin B. BDNF and 5−HT: a dynamic duo in age—related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 2004; 27: 589–94

    Article  PubMed  CAS  Google Scholar 

  24. Maisonpierre P, Belluscio L, Squinto S, et al. Neurotrophin−3: a neurotrophic factor related to NGF and BDNF. Science 1990; 247: 1446–51

    Article  PubMed  CAS  Google Scholar 

  25. Hallbook F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in xenopus ovary. Neuron 1991; 6: 845–58

    Article  PubMed  CAS  Google Scholar 

  26. Ip N, Ibanez C, Nye S, et al. Mammalian neurotrophin−4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci U S A 1992; 89: 3060–4

    Article  PubMed  CAS  Google Scholar 

  27. Cao L, Jiao X, Zuzga D, et al. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 2004; 36: 827–35

    Article  PubMed  CAS  Google Scholar 

  28. Zhou L, Shine H. Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury. J Neurosci Res 2003; 74: 221–6

    Article  PubMed  CAS  Google Scholar 

  29. Anlar B, Sullivan K, Feldman E. Insulin—like growth factor—I and central nervous system development. Horm Metab Res 1999; 31: 120–5

    Article  PubMed  CAS  Google Scholar 

  30. Anderson MF, Aberg MAI, Nilsson M, et al. Insulin—like growth factor—I and neurogenesis in the adult mammalian brain. Brain Res Dev Brain Res 2002; 134: 115–22

    Article  PubMed  CAS  Google Scholar 

  31. Russo VC, Gluckman PD, Feldman EL, et al. The insulin—like growth factor system and its pleiotropic functions in brain. Endocr Rev 2005; 26: 916–43

    Article  PubMed  CAS  Google Scholar 

  32. Fernandez S, Fernandez AM, Lopez-Lopez C, et al. Emerging roles of insulin—like growth factor—I in the adult brain. Growth Horm IGF Res 2007; 17: 89–95

    Article  PubMed  CAS  Google Scholar 

  33. Aberg N, Brywe K, Isgaard J. Aspects of growth hormone and insulin—like growth factor—I related to neuroprotection, regeneration, and functional plasticity in the adult brain. Sci World J 2006; 18: 53–80

    Google Scholar 

  34. Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal survival by the serine—threonine protein kinase Akt. Science 1997; 275: 661–5

    Article  PubMed  CAS  Google Scholar 

  35. Beck K, Powell-Braxton L, Widmer H, et al. Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin—containing neurons. Neuron 1995; 14: 717–30

    Article  PubMed  CAS  Google Scholar 

  36. Carson M, Behringer R, Brinster R, et al. Insulin—like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron 1993; 10: 729–40

    Article  PubMed  CAS  Google Scholar 

  37. Ye P, Li L, Richards RG, et al. Myelination is altered in insulin—like growth factor—I null mutant mice. J Neurosci 2002 Jul 15; 22 (14): 6041–51

    Google Scholar 

  38. Ding Q, Vaynman S, Akhavan M, et al. Insulin—like growth factor I interfaces with brain—derived neurotrophic factor—mediated synaptic plasticity to modulate aspects of exercise—induced cognitive function. Neuroscience 2006; 140: 823–33

    Article  PubMed  CAS  Google Scholar 

  39. Fernandez A, de la Vega A, Torres-Aleman A. Insulin—like growth factor I restores motor coordination in a rat model of cerebellar ataxia. Proc Natl Acad Sci USA 1998; 95: 1253–8

    Article  PubMed  CAS  Google Scholar 

  40. Leinninger GM, Backus C, Uhler MD, et al. Phosphatidylinositol 3−kinase and Akt effectors mediate insulin—like growth factor—I neuroprotection in dorsal root ganglia neurons. FASEB J 2004; 18: 1544–6

    PubMed  CAS  Google Scholar 

  41. Kaspar BK, Llado J, Sherkat N, et al. Retrograde viral delivery of IGF—I prolongs survival in a mouse ALS model. Science 2003; 301: 839–42

    Article  PubMed  CAS  Google Scholar 

  42. Vincent A, Mobley B, Hiller A, et al. IGF—I prevents glutamate—induced motor neuron programmed cell death. Neurol Dis 2004; 16: 407–16

    CAS  Google Scholar 

  43. Carro E, Trejo J, Gomez-Isla T, et al. Serum insulin—like growth factor I regulates brain amyloid— levels. Nat Med 2002; 8: 1390–7

    Article  PubMed  CAS  Google Scholar 

  44. Kermer P, Klocker N, Labes M, et al. Insulin—like growth factor I protects axotomized rat retinal ganglion cells from secondary death via PI3—K—dependent Akt phosphorylation and inhibition of caspase−3 in vivo. J Neurosci 2000; 20: 2–8

    PubMed  CAS  Google Scholar 

  45. Svensson J, Diez M, Engel J, et al. Endocrine, liver—derived IGF—I is of importance for spatial learning and memory in old mice. J Endocrinol 2006; 189: 617–27

    Article  PubMed  CAS  Google Scholar 

  46. Lupien S, Bluhm E, Ishii D. Systemic insulin—like growth factor—I administration prevents cognitive impairment in diabetic rats, and brain IGF regulates learning/memory in normal adult rats. J Neurosci Res 2003; 74: 512–23

    Article  PubMed  CAS  Google Scholar 

  47. Hoshaw B, Malberg J, Lucki I. Central administration of IGF—I and BDNF leads to long—lasting antidepressant—like effects. Brain Res 2005; 1037: 204–8

    Article  PubMed  CAS  Google Scholar 

  48. Yao D-L, Xia L, Hudson LD, et al. Insulin—like growth factor—I given subcutaneously reduces clinical deficits, decreases lesion severity and upregulates synthesis of myelin proteins in experimental autoimmune encephalomyelitis. Life Sci 1996; 58: 1301–6

    Article  PubMed  CAS  Google Scholar 

  49. Yao D, Liu X, Hudson L, et al. Insulin—like growth factor I treatment reduces demyelination and up—regulates gene expression of myelin—related proteins in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 1995; 92: 6190–4

    Article  PubMed  CAS  Google Scholar 

  50. Liu X, Yao D, Webster H. Insulin—like growth factor I treatment reduces clinical deficits and lesion severity in acute demyelinating experimental autoimmune encephalomyelitis. Mult Scler 1995; 1: 2–9

    PubMed  CAS  Google Scholar 

  51. Ye P, D’Ercole AJ. Insulin—like growth factor I protects oligodendrocytes from tumor necrosis factor—alpha—induced injury. Endocrinology 1999; 140: 3063–72

    Article  PubMed  CAS  Google Scholar 

  52. Leinninger G, Feldman E. Insulin—like growth factors in the treatment of neurological disease. Endocr Rev 2005; 9: 135–9

    CAS  Google Scholar 

  53. Probert L, Akassoglou K, Pasparakis M, et al. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system—specific expression of tumor necrosis factor. Proc Natl Acad Sci U S A 1995; 92: 11294–8

    Article  PubMed  CAS  Google Scholar 

  54. Akassoglou K, Probert L, Kontogeorgos G, et al. Astrocyte—specific but not neuron—specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice. J Immunol 1997; 158: 438–45

    PubMed  CAS  Google Scholar 

  55. Ye P, Kollias G, D’Ercole A. Insulin—like growth factor—I ameliorates demyelination induced by tumor necrosis factor—a in transgenic mice. J Neurosci Res 2007; 85: 712–22

    Article  PubMed  CAS  Google Scholar 

  56. Carro E, Nunez A, Busiguina S, et al. Circulating insulin—like growth factor I mediates effects of exercise on the brain. J Neurosci 2000; 20: 2926–33

    PubMed  CAS  Google Scholar 

  57. Carro E, Trejo J, Busiguina S, et al. Circulating insulin—like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 2001; 21: 5678–84

    PubMed  CAS  Google Scholar 

  58. Trejo JL, Carro E, Torres-Aleman I. Circulating insulin—like growth factor I mediates exercise—induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001; 21: 1628–34

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Rossi C, Angelucci A, Costantin L, et al. Brain—derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci 2006; 24: 1850–6

    Article  PubMed  Google Scholar 

  61. Schabitz W, Schwab S, Spranger M, et al. Intraventricular brain—derived neurotrophic factor reduces infarct size after focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1997; 17: 500–6

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  63. Xu X, Guenard V, Klritman N, et al. A combination of BDNF and NT−3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol 1995; 134: 261–72

    Article  PubMed  CAS  Google Scholar 

  64. Ye J, Houle J. Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol 1997; 143: 70–81

    Article  PubMed  CAS  Google Scholar 

  65. Mizuno M, Yamada K, Olariu A, et al. Involvement of brain—derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J Neurosci 2000; 20: 7116–21

    PubMed  CAS  Google Scholar 

  66. Alonso M, Monica RMV, Ivan I, et al. Signaling mechanisms mediating BDNF modulation of memory formation in vivo in the hippocampus. Cell Mol Neurobiol 2002; 22: 663–74

    Article  PubMed  CAS  Google Scholar 

  67. Alonso M, Vianna R, Depino A, et al. BDNF—triggered events in the rat hippocampus are required for both short— and long—term memory formation. Hippocampus 2002; 12: 551–60

    Article  PubMed  CAS  Google Scholar 

  68. Yan Q, Elliott J, Snider WD. Brain—derived neurotrophic factor rescues spinal motor neurons from axotomy—induced cell death. Nature 1992; 360: 753–5

    Article  PubMed  CAS  Google Scholar 

  69. Kishino A, Ishige Y, Tatsuno T, et al. BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth. Exp Neurol 1997; 144: 273–86

    Article  PubMed  CAS  Google Scholar 

  70. Mc Allister A, Katz L, Lo D. Neurotrophins and synaptic plasticity. Annu Rev Neurosci 1999; 22: 295–318

    Article  Google Scholar 

  71. Lu B. BDNF and activity dependent synaptic plasticity. Learn Mem 2003; 10: 86–98

    Article  PubMed  Google Scholar 

  72. Lu B. Acute and long—term synaptic modulation by neurotrophins. Prog Brain Res 2004; 146: 137–50

    PubMed  CAS  Google Scholar 

  73. Lom B, Cohen-Cory S. Brain derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal aborization in vivo. J Neurosci 1999; 19: 9928–38

    PubMed  CAS  Google Scholar 

  74. Yacoubian T, Lo D. Truncated and full length Trk B receptors regulate distinct modes of dendritic outgrowth. Nat Neurosci 2000; 3: 342–9

    Article  PubMed  CAS  Google Scholar 

  75. Alsina B, Vu T, Cohen-Cory S. Visualizing synapse formation in arborizing optic axons in vivo: dynamics and modulation by BDNF. Nat Neurosci 2001; 4: 1093–101

    Article  PubMed  CAS  Google Scholar 

  76. Lohof A, Ip N, Poo M. Potentiation of developing neuromuscular synapses by the neurotrophins NT−3 and BDNF. Nature 1993; 27: 350–3

    Article  Google Scholar 

  77. Kafitz K, Ross C, Thoenen H, et al. Neurotrophin—evoked rapid excitation through TrkB receptors. Nature 1999; 28: 918–21

    Google Scholar 

  78. Gomez-Pinilla F, Ying Z, Roy R, et al. Voluntary exercise induces a BDNF—mediated mechanism that promotes neuroplasticity. J Neurophysiol 2002; 88: 2187–95

    Article  PubMed  CAS  Google Scholar 

  79. Vaynman S, Gomez-Pinilla F. License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil Neural Repair 2005; 19: 283–95

    Article  PubMed  Google Scholar 

  80. Chen MJ, Russo-Neustadt AA. Exercise activates the phosphatidylinositol 3−kinase pathway. Mol Brain Res 2005; 135: 181–93

    Article  PubMed  CAS  Google Scholar 

  81. Vaynman S, Ying Z, Gomez-Pinilla F. Interplay between brain—derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic—plasticity. Neuroscience 2003; 122: 647–57

    Article  PubMed  CAS  Google Scholar 

  82. Griesbach GS, Hovda DA, Molteni R, et al. Voluntary exercise following traumatic brain injury: brain—derived neurotrophic factor upregulation and recovery of function. Neuroscience 2004; 125: 129–39

    Article  PubMed  CAS  Google Scholar 

  83. Macias M, Fehr S, Dwornik A, et al. Exercise increases mRNA levels for adhesion molecules N—CAM and L1 correlating with BDNF response. Neuroreport 2002; 13: 2527–30

    Article  PubMed  CAS  Google Scholar 

  84. Perreau V, Adlard P, Anderson A, et al. Exercise—induced gene expression changes in the rat spinal cord. Gene Expr 2005; 12: 107–21

    Article  PubMed  Google Scholar 

  85. Berchtold NC, Chinn G, Chou M, et al. Exercise primes a molecular memory for brain—derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 2005; 133: 853–61

    Article  PubMed  CAS  Google Scholar 

  86. Dupont-Versteegden E, Houlé J, Dennis R, et al. Exercise—induced gene expression in soleus muscle is dependent on time after spinal cord injury in rats. Muscle Nerve 2004; 29: 73–81

    Article  PubMed  CAS  Google Scholar 

  87. Sendtner M, Holtmann B, Kolbeck R, et al. Brain—derived neurotrophic factor prevents the death of motoneurons in new—born rats after nerve section. Nature 1992; 360: 757–9

    Article  PubMed  CAS  Google Scholar 

  88. Griesbeck O, Parsadanian A, Sendtner M, et al. Expression of neurotrophins in skeletal muscle: quantitative comparison and significance for motoneuron survival and maintenance of function. J Neurosci Res 1995; 42: 21–33

    Article  PubMed  CAS  Google Scholar 

  89. Koliatsos V, Clatterbuck R, Winslow J, et al. Evidence that brain—derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 1993; 10: 359–67

    Article  PubMed  CAS  Google Scholar 

  90. Funakoshi H, Frisen J, Barbany G, et al. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol 1993; 123: 455–65

    Article  PubMed  CAS  Google Scholar 

  91. Kishino A, Nakayama C. Enhancement of BDNF and activated ERK immunoreactivity in spinal motor neurons after peripheral administration of BDNF. Brain Res 2003; 964: 56–66

    Article  PubMed  CAS  Google Scholar 

  92. Copray S, Liem R, Brouwer N, et al. Contraction—induced muscle fiber damage is increased in soleus muscle of streptozotocin—diabetic rats and is associated with elevated expression of brain—derived neurotrophic factor mRNA in muscle fibers and activated satellite cells. Exp Neurol 2000; 161: 597–608

    Article  PubMed  CAS  Google Scholar 

  93. Liem R, Brouwer N, Copray J. Ultrastructural localisation of intramuscular expression of BDNF mRNA by silver—gold intensified non—radioactive in situ hybridisation. Histochem Cell Biol 2001; 116: 545–51

    Article  PubMed  CAS  Google Scholar 

  94. Gold SM, Schulz K-H, Hartmann S, et al. Basal serum levels and reactivity of nerve growth factor and brain—derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol 2003; 138: 99–105

    Article  PubMed  CAS  Google Scholar 

  95. Lommatzsch M, Zingler D, Schuhbaeck K, et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 2005; 26: 115–23

    Article  PubMed  CAS  Google Scholar 

  96. Levi-Montalcini R, Dal Toso R, della Valle F, et al. Update of the NGF saga. J Neurol Sci 1995; 130: 119–27

    Article  PubMed  CAS  Google Scholar 

  97. Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 2001; 24: 1217–81

    Article  PubMed  CAS  Google Scholar 

  98. Castren E, Pitkanen M, Sirvio J, et al. The induction of LTP increases BDNF and NGF mRNA but decreases NT−3 mRNA in the dentate gyrus. Neuroreport 1993; 4: 895–8

    Article  PubMed  CAS  Google Scholar 

  99. Hennigan A, O’callaghan RM, Kelly ÃM. Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans 2007; 35: 424–7

    Article  PubMed  CAS  Google Scholar 

  100. Prakash N, Cohen-Cory S, Frostig RD. Rapid and opposite effects of BDNF and NGF on the functional organization of the adult cortex in vivo. Nature 1996; 381: 702–6

    Article  PubMed  CAS  Google Scholar 

  101. Ramer MS, Priestley JV, Mc Mahon SB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000; 403: 312–6

    Article  PubMed  CAS  Google Scholar 

  102. Niewiadomska G, Baksalerska-Pazera M, Gasiorowska A, et al. Nerve growth factor differentially affects spatial and recognition memory in aged rats. Neurochem Res 2006; 31: 1481–90

    Article  PubMed  CAS  Google Scholar 

  103. Woolf NJ, Milov AM, Schweitzer ES, et al. Elevation of nerve growth factor and antisense knockdown of TrkA receptor during contextual memory consolidation. J Neurosci 2001; 21: 1047–55

    PubMed  CAS  Google Scholar 

  104. Tafreshi P. Nerve growth factor prevents demyelination, cell death and progression of the disease in experimental allergic encephalomyelitis. Iran J Allergy Asthma Immunol 2006; 5: 177–81

    CAS  Google Scholar 

  105. Radak Z, Toldy A, Szabo Z, et al. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochem Int 2006; 49: 387–92

    Article  PubMed  CAS  Google Scholar 

  106. Byrne A, Byrne DG. The effect of exercise on depression, anxiety and other mood states: a review. J Psychosom Res 1993; 37: 565–74

    Article  PubMed  CAS  Google Scholar 

  107. DiLorenzo TM, Bargman EP, Stucky-Ropp R, et al. Long—term effects of aerobic exercise on psychological outcomes. Prev Med 1999; 28: 75–85

    Article  Google Scholar 

  108. Knubben K, Reischies FM, Adli M, et al. A randomised, controlled study on the effects of a short—term endurance training programme in patients with major depression. Br J Sports Med 2007; 41: 29–33

    Article  PubMed  CAS  Google Scholar 

  109. Paffenbarger R, Lee I, Leung R. Physical activity and personal characteristics associated with depression and suicide in American college men. Acta Psychiatr Scand Suppl 1994; 377: 16–22

    Article  PubMed  Google Scholar 

  110. Duman RS. Neurotrophic factors and regulation of mood: role of exercise, diet and metabolism. Neurobiol Aging 2005; 26: 88–93

    Article  PubMed  CAS  Google Scholar 

  111. Russo-Neustadt A, Ha T, Ramirez R, et al. Physical activity antidepressant treatment combination: impact on brain—derived neurotrophic factor and behavior in an animal model. Behav Brain Res 2001; 120: 87–95

    Article  PubMed  CAS  Google Scholar 

  112. Garza AA, Ha TG, Garcia C, et al. Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain. Pharmacol Biochem Behav 2004; 77: 209–20

    Article  PubMed  CAS  Google Scholar 

  113. Russo-Neustadt AA, Chen MJ. Brain—derived neurotrophic factor and antidepressant activity. Curr Pharm Des 2005; 11: 1495–510

    Article  PubMed  CAS  Google Scholar 

  114. Bakshi R, Shaikh ZA, Miletich RS, et al. Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Mult Scler 2000; 6: 181–5

    PubMed  CAS  Google Scholar 

  115. Turner AP, Williams RM, Bowen JD, et al. Suicidal ideation in multiple sclerosis. Arch Phys Med Rehab 2006; 87: 1073–8

    Article  Google Scholar 

  116. Hesdorffer D, Hauser W, Annegers J, et al. Major depression is a risk factor for seizures in older adults. Ann Neurol 2000; 47: 246–9

    Article  PubMed  CAS  Google Scholar 

  117. Larson SL, Owens PL, Ford D, et al. Depressive disorder, dysthymia, and risk of stroke: thirteen—year follow—up from the Baltimore Epidemiologic Catchment Area study. Stroke 2001; 32: 1979–83

    Article  PubMed  CAS  Google Scholar 

  118. Colcombe SJ, Erickson KI, Raz N, et al. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci 2003; 58: 176–80

    Article  PubMed  Google Scholar 

  119. Colcombe SJ, Erickson KI, Scalf PE, et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci 2006; 61: 1166–70

    Article  PubMed  Google Scholar 

  120. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta—analytic study. Psychol Sci 2003; 14 (2): 125–30

    Article  PubMed  Google Scholar 

  121. Colcombe S, Kramer A, Erickson K, et al. Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci U S A 2004; 101: 3316–21

    Article  PubMed  CAS  Google Scholar 

  122. Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 2004; 20: 2580–90

    Article  PubMed  Google Scholar 

  123. Kramer AF, Erickson KI, Colcombe SJ. Exercise, cognition, and the aging brain. J Appl Physiol 2006; 101: 1237–42

    Article  PubMed  Google Scholar 

  124. Tyler WJ, Alonso M, Bramham CR, et al. From acquisition to consolidation: on the role of brain—derived neurotrophic factor signaling in hippocampal—dependent learning. Learn Mem 2002; 9: 224–37

    Article  PubMed  Google Scholar 

  125. Linnarsson S, Bjorklund A, Ernfors P. Learning deficit in BDNF mutant mice. Eur J Neurosci 1997; 9: 2581–7

    Article  PubMed  CAS  Google Scholar 

  126. Arango-Lasprilla J, DeLuca J, Chiaravalloti N. Neuropsychological profile of multiple sclerosis. Psicothema 2007; 19: 1–6

    PubMed  Google Scholar 

  127. Rao S, Leo G, Bernardin L, et al. Cognitive dysfunction in multiple sclerosis: I. Frequency, patterns, and prediction. Neurology 1991; 41: 685–91

    Article  PubMed  CAS  Google Scholar 

  128. Bobholz JA, Rao SM. Cognitive dysfunction in multiple sclerosis: a review of recent developments. Curr Opin Neurol 2003; 16: 283–8

    Article  PubMed  Google Scholar 

  129. Staffen W, Mair A, Zauner H, et al. Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task. Brain 2002; 125: 1275–82

    Article  PubMed  CAS  Google Scholar 

  130. Filippi M, Rocca MA, Mezzapesa DM, et al. A functional MRI study of cortical activations associated with object manipulation in patients with MS. Neuroimage 2004; 21: 1147–54

    Article  PubMed  Google Scholar 

  131. Prakash RS, Snook EM, Erickson KI, et al. Cardiorespiratory fitness: a predictor of cortical plasticity in multiple sclerosis. Neuroimage 2007; 34: 1238–44

    Article  PubMed  Google Scholar 

  132. Mattson M, Liu D. Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders. Neuromolecular Med 2002; 2: 215–31

    Article  PubMed  CAS  Google Scholar 

  133. LeVine SM. The role of reactive oxygen species in the pathogenesis of multiple sclerosis. Med Hypotheses 1992; 39: 271–4

    Article  Google Scholar 

  134. Ferretti G, Bacchetti T, Principi F, et al. Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity. Mult Scler 2005; 11: 677–82

    Article  PubMed  CAS  Google Scholar 

  135. Radak Z, Taylor A, Ohno H, et al. Adaptation to exercise—induced oxidative stress: from muscle to brain. Exerc Immunol Rev 2001; 7: 90–107

    PubMed  CAS  Google Scholar 

  136. Mattson M, Scheff S. Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy. J Neurotrauma 1994; 11: 3–33

    Article  PubMed  CAS  Google Scholar 

  137. Guo ZH, Mattson MP. Neurotrophic factors protect cortical synaptic terminals against amyloid— and oxidative stress—induced impairment of glucose transport, glutamate transport and mitochondrial function. Cereb Cortex 2000; 10: 50–7

    Article  PubMed  CAS  Google Scholar 

  138. Wu A, Ying Z, Gomez-Pinilla F. The interplay between oxidative stress and brain—derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci 2004; 19: 1699–707

    Article  PubMed  Google Scholar 

  139. Nistico G, Ciriolo M, Fiskin K, et al. NGF restores decrease in catalase activity and increases superoxide dismutase and glutathione peroxidase activity in the brain of aged rats. Free Radic Biol Med 1992; 12: 177–81

    Article  PubMed  CAS  Google Scholar 

  140. Kiraly M, Kiraly S. The effect of exercise on hippocampal integrity: review of recent research. Int J Psychiatry Med 2005; 35: 75–89

    Article  PubMed  Google Scholar 

  141. Arumugam TV, Gleichmann M, Tang S-C, et al. Hormesis/preconditioning mechanisms, the nervous system and aging. Ageing Res Rev 2006; 5: 165–78

    Article  PubMed  CAS  Google Scholar 

  142. Radak Z, Chung H, Goto S. Exercise and hormesis: oxidative stress—related adaptation for successful aging. Biogerontology 2005; 6: 71–5

    Article  PubMed  CAS  Google Scholar 

  143. Mattson MP. Neuronal life—and—death signaling, apoptosis, and neurodegenerative disorders. Antioxid Redox Signal 2006; 8: 1997–2006

    Article  PubMed  CAS  Google Scholar 

  144. Gomez-Pinilla F. The influences of diet and exercise on mental health through hormesis. Ageing Res Rev. Epub 2007 May 5

    Google Scholar 

  145. Radak Z, Chung HY, Koltai E, et al. Exercise, oxidative stress and hormesis. Ageing Res Rev. Epub 2007 Aug 2

    Google Scholar 

  146. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25: 295–301

    Article  PubMed  CAS  Google Scholar 

  147. Sim YJ, Kim H, Kim JY, et al. Long—term treadmill exercise overcomes ischemia—induced apoptotic neuronal cell death in gerbils. Physiol Behav 2005; 84: 733–8

    Article  PubMed  CAS  Google Scholar 

  148. Dishman RK, Berthoud HR, Booth FW, et al. Neurobiology of exercise. Obesity (Silver Spring) 2006; 14: 345–56

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Rudy Dressendorfer for his editorial contributions. We also thank Sean McCoy and Darpan Patel for assistance in preparing this manuscript. We thank people living with multiple sclerosis who provided inspiration for this manuscript. No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lesley J. White.

Rights and permissions

Reprints and permissions

About this article

Cite this article

White, L.J., Castellano, V. Exercise and Brain Health — Implications for Multiple Sclerosis. Sports Med 38, 91–100 (2008). https://doi.org/10.2165/00007256-200838020-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-200838020-00001

Keywords

Navigation