NeuroMolecular Medicine

, Volume 10, Issue 2, pp 99–107 | Cite as

Growth Factors as Mediators of Exercise Actions on the Brain

  • M. Llorens-Martín
  • I. Torres-Alemán
  • José L. TrejoEmail author
Original Paper


Physical exercise has long been recognized as highly beneficial for brain and body health. The molecular mechanisms responsible for translation of exercise stimuli in the brain have claimed attention due to mounting evidence for the neuroprotective actions of the exercise and its positive effects in preventing both ageing and neurodegenerative disease. These molecular mediators are currently under investigation with new tools able to yield deep insights into the neurobiology of exercise. In the present work we focus on the evidence pertaining to the mediation of exercise effects by insulin-like growth factor 1 (IGF1), as recent reports suggest that this growth factor shows brain area-specific, temporal rank-sensitive, and behavioural task-dependent features in response to exercise.


Insulin-like growth factor 1 Physical exercise Hippocamus-dependent learning Adult hippocampal neurogenesis Cognitive impairment 


  1. Aberg, M. A., Aberg, N. D., Hedbacker, H., et al. (2000). Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. Journal of Neuroscience, 20, 2896–2903PubMedGoogle Scholar
  2. Aberg, N. D., Brywe, K. G., & Isgaard, J. (2006). Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. Scientific World Journal, 6, 53–80.PubMedGoogle Scholar
  3. Adkins, D. L., Boychuk, J., & Remple, M. S., et al. (2006). Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord. Journal of Applied Physiology, 101, 1776–1782.PubMedCrossRefGoogle Scholar
  4. Aleman, A., Verhaar, H.J., de Haan, E. H., et al. (1999). Insulin-like growth factor-I and cognitive function in healthy older men. Journal of Clinical Endocrinology and Metabolism, 84, 471–475.PubMedCrossRefGoogle Scholar
  5. Ang, E. T., Wong, P. T., Moochhala, S., et al. (2003). Neuroprotection associated with running: Is it a result of increased endogenous neurotrophic factors? Neuroscience, 118, 335–345.PubMedCrossRefGoogle Scholar
  6. Arwert, L. I., Deijen, J. B., & Drent, M. L. (2005). The relation between insulin-like growth factor I levels and cognition in healthy elderly: A meta-analysis. Growth Hormone & IGF Research, 15, 416–422.CrossRefGoogle Scholar
  7. Beck, K. D., Powell-Braxton, L., Widmer, H. R., et al. (1995). Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron, 14, 717–730.PubMedCrossRefGoogle Scholar
  8. Bilak, M. M., Corse, A. M., & Kuncl, R. W. (2001). Additivity and potentiation of IGF-I and GDNF in the complete rescue of postnatal motor neurons. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 2, 83–91.CrossRefPubMedGoogle Scholar
  9. Black, J. E., Isaacs, K. R., Anderson, B. J., et al. (1990). Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proceedings of the National Academy of Sciences of the United States of America, 87, 5568–5572.PubMedCrossRefGoogle Scholar
  10. Breese, C. R., Ingram, R. L., & Sonntag, W. E. (1991). Influence of age and long-term dietary restriction on plasma insulin-like growth factor-1 (IGF-1), IGF-1 gene expression, and IGF-1 binding proteins. Journal of Gerontology, 46, B180–B187.PubMedGoogle Scholar
  11. Bulow, B., Hagmar, L., Orbaek, P., et al. (2002). High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease. Clinical Endocrinology, 56, 183–193.PubMedCrossRefGoogle Scholar
  12. Busiguina, S., Fernandez, A. M., Barrios, V., et al. (2000). Neurodegeneration is associated to changes in serum insulin-like growth factors. Neurobiology of Disease, 7, 657–665.PubMedCrossRefGoogle Scholar
  13. Carro, E., Nunez, A., Busiguina, S., et al. (2000). Circulating insulin-like growth factor I mediates effects of exercise on the brain. Journal of Neuroscience, 20, 2926–2933.PubMedGoogle Scholar
  14. Carro, E., Spuch, C., Trejo, J. L., et al. (2005). Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I. Journal of Neuroscience, 25, 10884–10893.PubMedCrossRefGoogle Scholar
  15. Carro, E., Trejo, J. L., Busiguina, S., et al. (2001). Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. Journal of Neuroscience, 21, 5678–5684.PubMedGoogle Scholar
  16. Carro, E., Trejo, J. L., Gomez-Isla, T., et al. (2002). Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nature Medicine, 8, 1390–1397.PubMedCrossRefGoogle Scholar
  17. Carro, E., Trejo, J. L., Nunez, A., et al. (2003). Brain repair and neuroprotection by serum insulin-like growth factor I. Molecular Neurobiology, 27, 153–162.PubMedCrossRefGoogle Scholar
  18. Carson, M. J., Behringer, R. R., Brinster, R. L., et al. (1993). Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron, 10, 729–740.PubMedCrossRefGoogle Scholar
  19. Castro-Alamancos, M. A., & Torres-Aleman, I. (1993) Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I. Proceedings of the National Academy of Sciences of the United States of America, 90, 7386–7390.PubMedCrossRefGoogle Scholar
  20. Chen, M. J., & Russo-Neustadt, A. A. (2007). Running exercise- and antidepressant-induced increases in growth and survival-associated signaling molecules are IGF-dependent. Growth Factors, 25(2), 118-131.PubMedCrossRefGoogle Scholar
  21. Cheng, H. L., & Feldman, E. L. (1998). Bidirectional regulation of p38 kinase and c-Jun N-terminal protein kinase by insulin-like growth factor-I. The Journal Biological Chemistry, 273, 14560–14565.CrossRefGoogle Scholar
  22. Chrysis, D., Calikoglu, A. S., Ye, P., et al. (2001) Insulin-like growth factor-I overexpression attenuates cerebellar apoptosis by altering the expression of Bcl family proteins in a developmentally specific manner. The Journal of Neuroscience, 21, 1481–1489.PubMedGoogle Scholar
  23. Cotman, C. W., & Berchtold, N. C. (2002). Exercise: A behavioral intervention to enhance brain health and plasticity. Trends in Neurosciences, 25, 295–301.PubMedCrossRefGoogle Scholar
  24. Cotman, C. W., Berchtold, N. C., & Christie, L. A. (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30, 464–472.PubMedCrossRefGoogle Scholar
  25. Davila, D., Piriz, J., Trejo, J. L., et al. (2007). Insulin and insulin-like growth factor I signalling in neurons. Frontiers in Bioscience 12, 3194–3202.PubMedCrossRefGoogle Scholar
  26. Deuschle, M., Blum, W. F., Frystyk, J., et al. (1998). Endurance training and its effect upon the activity of the GH-IGFs system in the elderly. International Journal of Sports Medicine, 19, 250–254.PubMedCrossRefGoogle Scholar
  27. Dik, M. G., Pluijm, S. M., Jonker, C., et al. (2003). Insulin-like growth factor I (IGF-I) and cognitive decline in older persons. Neurobiology of Aging, 24, 573–581.PubMedCrossRefGoogle Scholar
  28. Ding, Q., Vaynman, S., Akhavan, M., et al. (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.PubMedCrossRefGoogle Scholar
  29. Dishman, R. K., Berthoud, H. R., Booth, F. W., et al. (2006). Neurobiology of exercise. Obesity (Silver Spring), 14, 345–356.CrossRefGoogle Scholar
  30. Dore, S., Kar, S., & Quirion, R. (1997). Insulin-like growth factor I protects and rescues hippocampal neurons against beta-amyloid- and human amylin-induced toxicity. Proceedings of the National Academy of Sciences of the United States of America, 94, 4772–4777.PubMedCrossRefGoogle Scholar
  31. Eliakim, A., Brasel, J. A., & Cooper, D. M. (1999). GH response to exercise: assessment of the pituitary refractory period, and relationship with circulating components of the GH-IGF-I axis in adolescent females. Journal of Pediatric Endocrinology & Metabolism, 12, 47–55.Google Scholar
  32. Eliakim, A., Brasel, J. A., Mohan, S., et al. (1998). Increased physical activity and the growth hormone-IGF-I axis in adolescent males. The American Journal of Physiology, 275, R308–R314.PubMedGoogle Scholar
  33. Fabel, K., Fabel, K., Tam, B., et al. (2003). VEGF is necessary for exercise-induced adult hippocampal neurogenesis. The European Journal of Neuroscience, 18, 2803–2812.PubMedCrossRefGoogle Scholar
  34. Fernandez, A. M., de la Vega, A. G., & Torres-Aleman, I. (1998). Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia. Proceedings of the National Academy of Sciences of the United States of America, 95, 1253–1258.PubMedCrossRefGoogle Scholar
  35. Fernandez, A. M., Gonzalez de la Vega, A. G., Planas, B., et al. (1999). Neuroprotective actions of peripherally administered insulin-like growth factor I in the injured olivo-cerebellar pathway. The European Journal of Neuroscience, 11, 2019–2030.PubMedCrossRefGoogle Scholar
  36. Garcia-Segura, L. M., Duenas, M., Fernandez-Galaz, M. C., et al. (1996). Interaction of the signalling pathways of insulin-like growth factor-I and sex steroids in the neuroendocrine hypothalamus. Hormone Research, 46, 160–164.PubMedCrossRefGoogle Scholar
  37. Giannakou, M. E., & Partridge, L. (2007). Role of insulin-like signalling in Drosophila lifespan. Trends in Biochemical Sciences, 32, 180–188.PubMedCrossRefGoogle Scholar
  38. Guan, J., Bennet, L., George, S., et al. (2001) Insulin-like growth factor-1 reduces postischemic white matter injury in fetal sheep. Journal of Cerebral Blood Flow and Metabolism, 21, 493–502.PubMedGoogle Scholar
  39. Hantai, D., Akaaboune, M., Lagord, C., et al. (1995). Beneficial effects of insulin-like growth factor-I on wobbler mouse motoneuron disease. Journal of the Neurological Science, 129(Suppl), 122–126.CrossRefGoogle Scholar
  40. Holzenberger, M., Dupont, J., Ducos, B., et al. (2003). IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature, 421, 182–187.PubMedCrossRefGoogle Scholar
  41. Hoshaw, B. A., Malberg, J. E., & Lucki, I. (2005). Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects. Brain Research, 1037, 204–208.PubMedCrossRefGoogle Scholar
  42. Humbert, S., Bryson, E. A., Cordelieres, F. P., et al. (2002) The IGF-1/Akt pathway is neuroprotective in Huntington’s disease and involves Huntingtin phosphorylation by Akt. Developmental Cell, 2, 831–837.PubMedCrossRefGoogle Scholar
  43. Jones, T. A., Chu, C. J., Grande, L. A., et al. (1999). Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. Journal of Neuroscience, 19, 10153–10163.PubMedGoogle Scholar
  44. Kalmijn, S., Janssen, J. A., Pols, H. A., et al. (2000). A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly. Journal of Clinical Endocrinology and Metabolism, 85, 4551–4555.PubMedCrossRefGoogle Scholar
  45. Karsten, S. L., & Geschwind, D. H. (2005). Exercise your amyloid. Cell, 120, 572–574.PubMedCrossRefGoogle Scholar
  46. Kenyon, C. (2004). My adventures with genes from the fountain of youth. Harvey Lectures, 100, 29–70.PubMedGoogle Scholar
  47. Koopmans, G. C., Brans, M., Gomez-Pinilla, F., et al. (2006). Circulating insulin-like growth factor I and functional recovery from spinal cord injury under enriched housing conditions. European Journal of Neurosciences, 23, 1035–1046.CrossRefGoogle Scholar
  48. Koponen, E., Rantamaki, T., Voikar, V., et al. (2005). Enhanced BDNF signaling is associated with an antidepressant-like behavioral response and changes in brain monoamines. Cellular and Molecular Neurobiology, 25, 973–980.PubMedCrossRefGoogle Scholar
  49. Landi, F., Capoluongo, E., Russo, A., et al. (2007). Free insulin-like growth factor-I and cognitive function in older persons living in community. Growth Hormone & IGF Research, 17, 58–66.CrossRefGoogle Scholar
  50. Le, G. M., Steensland, P., Le, G. P., et al. (2002). Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N-methyl-D-aspartate receptor subunits gene transcripts in male rats. Proceedings of the National Academy of Sciences of the United States of America, 99, 7119–7123.CrossRefGoogle Scholar
  51. Leifke, E., Gorenoi, V., Wichers, C., et al. (2000). Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort. Clinical Endocrinology, 53, 689–695.PubMedCrossRefGoogle Scholar
  52. Lijffijt, M., Van Dam, P. S., Kenemans, J. L., et al. (2003). Somatotropic-axis deficiency affects brain substrates of selective attention in childhood-onset growth hormone deficient patients. Neuroscience Letters, 353, 123–126.PubMedCrossRefGoogle Scholar
  53. Lommatzsch, M., Braun, A., Mannsfeldt, A., et al. (1999). Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions. The American Journal of Pathology, 155, 1183–1193.PubMedGoogle Scholar
  54. Lopez-Lopez, C., Leroith, D., & Torres-Aleman, I. (2004). Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proceedings of the National Academy of Sciences of the United States of America, 101, 9833–9838.PubMedCrossRefGoogle Scholar
  55. Markowska, A. L., Mooney, M., & Sonntag, W. E. (1998). Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience, 87, 559–569.PubMedCrossRefGoogle Scholar
  56. Miyata, M., Kim, H. T., Hashimoto, K., et al. (2001). Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C beta4 mutant mice. European Journal of Neurosciences, 13, 1945–1954.CrossRefGoogle Scholar
  57. Monteggia, L. M., Barrot, M., Powell, C. M., et al. (2004). Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proceedings of the National Academy of Sciences of the United States of America, 101, 10827–10832.PubMedCrossRefGoogle Scholar
  58. Neves-Pereira, M., Mundo, E., Muglia, P., et al. (2002). The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: Evidence from a family-based association study. American Journal of Human Genetics, 71, 651–655.PubMedCrossRefGoogle Scholar
  59. Nieto-Bona, M. P., Garcia-Segura, L. M., & Torres-Aleman, I. (1997). Transynaptic modulation by insulin-like growth factor I of dendritic spines in Purkinje cells. International Journal of Developmental Neuroscience, 15, 749–754.PubMedCrossRefGoogle Scholar
  60. Nunez, A., Carro, E., & Torres-Aleman, I. (2003). Insulin-like growth factor I modifies electrophysiological properties of rat brain stem neurons. Journal of Neurophysiology, 89, 3008–3017.PubMedCrossRefGoogle Scholar
  61. Okereke, O., Kang, J. H., Ma, J., et al. (2007). Plasma IGF-I levels and cognitive performance in older women. Neurobiology of Aging, 28, 135–142.PubMedCrossRefGoogle Scholar
  62. O’Kusky, J. R., Ye, P., & D’Ercole, A. J. (2000). Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. Journal of Neuroscience, 20, 8435–8442.PubMedGoogle Scholar
  63. Ono, M., Itakura, Y., Nonomura, T., et al. (2000). Intermittent administration of brain-derived neurotrophic factor ameliorates glucose metabolism in obese diabetic mice. Metabolism, 49, 129–133.PubMedCrossRefGoogle Scholar
  64. Pan, W., Banks, W. A., & Kastin, A. J. (1998) Permeability of the blood-brain barrier to neurotrophins. Brain Research, 788, 87–94.PubMedCrossRefGoogle Scholar
  65. Ploughman, M., Attwood, Z., White, N., et al. (2007). Endurance exercise facilitates relearning of forelimb motor skill after focal ischemia. European Journal of Neuroscience, 25, 3453–3460.PubMedCrossRefGoogle Scholar
  66. Ploughman, M., Granter-Button, S., Chernenko, G., et al. (2005). Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia. Neuroscience, 136, 991–1001.PubMedCrossRefGoogle Scholar
  67. Pulford, B. E., Whalen, L.R., & Ishii, D. N. (1999). Peripherally administered insulin-like growth factor-I preserves hindlimb reflex and spinal cord noradrenergic circuitry following a central nervous system lesion in rats. Experimental Neurology, 159, 114–123.PubMedCrossRefGoogle Scholar
  68. Roelen, C. A., de Vries, W. R., Koppeschaar, H. P., et al. (1997). Plasma insulin-like growth factor-I and high affinity growth hormone-binding protein levels increase after two weeks of strenuous physical training. International Journal of Sports Medicine, 18, 238–241.PubMedCrossRefGoogle Scholar
  69. Rollero, A., Murialdo, G., Fonzi, S., et al. (1998). Relationship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects. Neuropsychobiology, 38, 73–79.PubMedCrossRefGoogle Scholar
  70. Rosenfeld, R. D., Zeni, L., Haniu, M., et al. (1995). Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expression and Purification, 6, 465–471.PubMedCrossRefGoogle Scholar
  71. Russo, V.C., Gluckman, P. D., Feldman, E. L., et al. (2005) The insulin-like growth factor system and its pleiotropic functions in brain. Endocrine Reviews, 26, 916–943.PubMedCrossRefGoogle Scholar
  72. Serrano, T., Lorigados, L. C., et al. (1996) Nerve growth factor levels in normal human sera. Neuroreport, 8, 179–181.PubMedCrossRefGoogle Scholar
  73. Shirayama, Y., Chen, A. C., Nakagawa, S., et al. (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Journal of Neurosciences, 22, 3251–3261.Google Scholar
  74. Smith, A. D., & Zigmond, M. J. (2003). Can the brain be protected through exercise? Lessons from an animal model of parkinsonism. Experimental Neurology, 184, 31–39.PubMedCrossRefGoogle Scholar
  75. Sonntag, W. E., Lynch, C. D., Cooney, P. T., et al. (1997) Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology, 138, 3515–3520.PubMedCrossRefGoogle Scholar
  76. Stummer, W., Weber, K., Tranmer, B., et al. (1994) Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia. Stroke, 25, 1862–1869.PubMedGoogle Scholar
  77. Svensson, J., Diez, M., Engel, J., et al. (2006). Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice. The Journal of Endocrinology, 189, 617–627.PubMedCrossRefGoogle Scholar
  78. Tissandier, O., Peres, G., Fiet, J., et al. (2001). Testosterone, dehydroepiandrosterone, insulin-like growth factor 1, and insulin in sedentary and physically trained aged men. European Journal of Applied Physiology, 85, 177–184.PubMedCrossRefGoogle Scholar
  79. Torres-Aleman, I. (2000). Serum growth factors and neuroprotective surveillance: Focus on IGF-1. Molecular Neurobiology, 21, 153–160.PubMedCrossRefGoogle Scholar
  80. Trejo, J. L., Carro, E., Garcia-Galloway, E., et al. (2004a). Role of insulin-like growth factor I signaling in neurodegenerative diseases. Journal of Molecular Medicine, 82, 156–162.PubMedCrossRefGoogle Scholar
  81. Trejo, J. L., Carro, E., Lopez-Lopez, C., et al. (2004b). Role of serum insulin-like growth factor I in mammalian brain aging. Growth Hormone & IGF Research, 14(Suppl A), S39–S43.CrossRefGoogle Scholar
  82. Trejo, J. L., Carro, E., Nunez, A., et al. (2002). Sedentary life impairs self-reparative processes in the brain: the role of serum insulin-like growth factor-I. Reviews in the Neurosciences, 13, 365–374.PubMedGoogle Scholar
  83. Trejo, J. L., 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. The Journal of Neuroscience, 21, 1628–1634.PubMedGoogle Scholar
  84. Trejo, J. L., Llorens-Martin, M., & Torres-Aleman, I. (2008). The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Molecular and Cellular Neurosciences, 37, 402–411.PubMedCrossRefGoogle Scholar
  85. Trejo, J. L., Piriz, J., Llorens-Martin, M. V., et al. (2007). Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Molecular Psychiatry, 12, 1118–1128.PubMedCrossRefGoogle Scholar
  86. Vaynman, S., Ying, Z., & Gomez-Pinilla, F. (2004). Exercise induces BDNF and synapsin I to specific hippocampal subfields. Journal of Neuroscience Research, 76, 356–362.PubMedCrossRefGoogle Scholar
  87. Vaynman, S. S., Ying, Z., Yin, D., et al. (2006) Exercise differentially regulates synaptic proteins associated to the function of BDNF. Brain Research, 1070, 124–130.PubMedCrossRefGoogle Scholar
  88. Wallace, J. D., Cuneo, R. C., Baxter, R., et al. (1999). Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: A potential test for GH abuse in sport. The Journal of Clinical Endocrinology and Metabolism, 84, 3591–3601.PubMedCrossRefGoogle Scholar
  89. Welsh, J. P., Yamaguchi, H., Zeng, X. H., et al. (2005). Normal motor learning during pharmacological prevention of Purkinje cell long-term depression. Proceedings of the National Academy of Sciences of the United States of America, 102, 17166–17171.PubMedCrossRefGoogle Scholar
  90. Yakar, S., Liu, J. L., Stannard, B., et al. (1999). Normal growth and development in the absence of hepatic insulin-like growth factor I. Proceedings of the National Academy of Sciences of the United States of America, 96, 7324–7329.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  • M. Llorens-Martín
    • 1
  • I. Torres-Alemán
    • 1
  • José L. Trejo
    • 1
    Email author
  1. 1.Instituto Cajal, CSICMadridSpain

Personalised recommendations