Advertisement

Implication of Oxidative Stress, Aging, and Inflammatory Processes in Neurodegenerative Diseases: Growth Factors as Therapeutic Approach

  • Macarena Lorena Herrera
  • Eugenia Falomir-Lockhart
  • Franco Juan Cruz Dolcetti
  • Nathalie Arnal
  • María José Bellini
  • Claudia Beatriz HereñúEmail author
Chapter

Abstract

The incidence of neurodegenerative diseases is increasing progressively, and unfortunately the molecular mechanisms that lead to them are still unknown. Several studies are advancing in the comprehension of the processes involved in the establishment of the neurodegeneration. In this sense, the current approaches are focused on genes associated with the neurodegenerative diseases, reactional gliosis or microglial activation, pro-inflammatory cytokine production, IL-6 increase as a transcription factor, growth factor decrease, mitochondrial dysfunction, antioxidant defense system, cellular metabolism, protein degradation/aggregation, and oxidative stress triggering redox-dependent signals, among others. Parkinson’s and Alzheimer’s diseases show an increased diagnosis worldwide and are examples of deleterious effects associated with aging.

The present chapter is focused on the implication of the oxidative stress, aging, and inflammation processes on neurodegenerative alterations that lead to neuronal dysfunctions, tissue disturbances, and motor-cognitive disorders. In regard to this, the neurotrophic factors of clinical interest prevent the degeneration and enhance recovery of remaining neurons. Among them, insulin-like growth factor 1 (IGF-1), which is strongly induced by microglial cells after different insults such as ischemia, cortical injury, and inflammatory processes, is emerging as a powerful neuroprotective molecule. For this reason, we will close this chapter with the implications of IGF-1 on neurodegenerative diseases as a key neuroprotective and neuromodulator molecule.

Keywords

Inflammation Aging Neurodegeneration Neurotrophic factors 

References

  1. 1.
    Pope S, Land JM, Heales SJ. Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target? Biochim Biophys Acta. 2008;1767(7–8):782–9.Google Scholar
  2. 2.
    Spano M, Signorelli M, Vitaliani R, Aguglia E, Giometto B. The possible involvement of mitochondrial dysfunctions in Lewy body dementia: a systematic review. Funct Neurol. 2015;30(3):151–8.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Tönnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis. 2017;57(4):1105–21.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1–13.PubMedGoogle Scholar
  5. 5.
    Giachin G, Bouverot R, Acajjaoui S, Pantalone S, Soler-López M. Dynamics of human mitochondrial complex I assembly: implications for neurodegenerative diseases. Front Mol Biosci. 2016;3:43.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Berndt N, Holzhütter HG, Bulik S. Implications of enzyme deficiencies on mitochondrial energy metabolism and reactive oxygen species formation of neurons involved in rotenone-induced Parkinson’s disease: a model-based analysis. FEBS J. 2013;279(20):5079–92.Google Scholar
  7. 7.
    Zhang L, Zhang S, Maezawa I, Trushin S, Minhas P, Pinto M, Jin LW, Prasain K, Nguyen TD, Yamazaki Y, Kanekiyo T, Bu G, Gateno B, Chang KO, Nath KA, Nemutlu E, Dzeja P, Pang YP, Hua DH, Trushina E. Modulation of mitochondrial complex I activity averts cognitive decline in multiple animal models of familial Alzheimer’s disease. EBioMedicine. 2015;2(4):293–305.Google Scholar
  8. 8.
    Sipos I, Tretter L, Adam-Vizi V. Quantitative relationship between inhibition of respiratory complexes and formation of reactive oxygen species in isolated nerve terminals. J Neurochem. 2003;82(1):112–8.Google Scholar
  9. 9.
    Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondrial complex I deficiency in Parkinson’s disease. Lancet. 1978;1(8539):1268.Google Scholar
  10. 10.
    Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA. Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci. 2001;21(9):3017–23.PubMedGoogle Scholar
  11. 11.
    Cristalli DO, Arnal N, Marra FA, de Alaniz MJ, Marra CA. Peripheral markers in neurodegenerative patients and their first-degree relatives. J Neurol Sci. 2012;314(1–2):48–56.PubMedGoogle Scholar
  12. 12.
    Avetisyan AV, Samokhin AN, Alexandrova IY, Zinovkin RA, Simonyan RA, Bobkova NV. Mitochondrial dysfunction in neocortex and hippocampus of olfactory bulbectomized mice, a model of Alzheimer’s disease. Biochemistry (Mosc). 2016;80(6):605–23.Google Scholar
  13. 13.
    Abeti R, Abramov AY, Duchen MR. Beta-amyloid activates PARP causing astrocytic metabolic failure and neuronal death. Brain. 2011;134(Pt 6):1648–71.Google Scholar
  14. 14.
    Delgado-Camprubi M, Esteras N, Soutar MP, Plun-Favreau H, Abramov AY. Deficiency of Parkinson’s disease-related gene Fbxo7 is associated with impaired mitochondrial metabolism by PARP activation. Cell Death Differ. 2017;24(1):120–31.PubMedGoogle Scholar
  15. 15.
    Ransohoff RM, Brown MA. Innate immunity in the central nervous system. J Clin Invest. 2012;122:1163–7.Google Scholar
  16. 16.
    Sierra A, Encinas JM, Deudero JJP, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell. 2010;7:482–94.Google Scholar
  17. 17.
    Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, Yamashita T. Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci. 2013;16:543–51.PubMedGoogle Scholar
  18. 18.
    Xia CY, Zhang S, Gao Y, Wang ZZ, Chen NH. Selective modulation of microglia polarization to M2 phenotype for stroke treatment. Int Immunopharmacol. 2015;25(2):376–81.Google Scholar
  19. 19.
    Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(7):35.Google Scholar
  20. 20.
    O’Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011;34:184–204.Google Scholar
  21. 21.
    Phani S, Loike JD, Przedborski S. Neurodegeneration and inflammation in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18:S207–9.PubMedGoogle Scholar
  22. 22.
    Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord. 2012;27:1082–90.Google Scholar
  23. 23.
    Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:908–24.Google Scholar
  24. 24.
    McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflamm. 2008;5:45.Google Scholar
  25. 25.
    Brown GC, Vilalta A. How microglia kill neurons. Brain Res. 2015;1618:287–96.Google Scholar
  26. 26.
    Franco R, Fernandez-Suarez D. Alternatively activated microglia and macrophages in the central nervous system. Prog Neurobiol. 2015;131:64–85.Google Scholar
  27. 27.
    Lunenfeld B. An aging world- demographics and challenges. Gynecol Endocrinol. 2008;24:1.PubMedGoogle Scholar
  28. 28.
    He W, Sengupta M, Velkoff VA, et al. 641 in the United States: 2005. Washington, DC: National Institute on Aging; U.S. Census Bureau; 2005.Google Scholar
  29. 29.
    Moll L, El-Ami T, Cohen E. Selective manipulation of aging: a novel strategy for the treatment of neurodegenerative disorders. Swiss Med Wkly. 2014;144:w13907.Google Scholar
  30. 30.
    Seidler RD, Bernard JA, Burutolu TB, Fling BW, Gordon M, Gwin J, Kwak Y, Lipps DB. Motor control and aging: links to age-related brain structural, functional and biomechanical effects. Neurosci Biobehav Rev. 2011;34(5):711–23.Google Scholar
  31. 31.
    Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, et al. Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex. 2005;15(11):1666–88.Google Scholar
  32. 32.
    Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS. A voxel-based morphometric study of ageing in 464 normal adult human brains. NeuroImage. 2001;14(1 Pt 1):21–36.PubMedGoogle Scholar
  33. 33.
    Courchesne E, Chisum HJ, Townsend J, Cowles A, Covington J, Egaas B, et al. Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology. 2000;216(3):662–81.Google Scholar
  34. 34.
    Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003;23(8):3294–301.Google Scholar
  35. 35.
    Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RS, Busa E, et al. Thinning of the cerebral cortex in aging. Cereb Cortex. 2014;14(7):711–30.Google Scholar
  36. 36.
    Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev Neurosci. 2006;7:30–40.PubMedGoogle Scholar
  37. 37.
    Castellano JM, Mosher KI, Abbey RJ, McBride AA, James ML, Berdnik D, Shen JC, Zou B, Xie XS, Tingle M, Hinkson IV, Angst MS, Wyss-Coray T. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature. 2017;544(7541):487–91.Google Scholar
  38. 38.
    Vanguilder HD, Freeman WM. The hippocampal neuroproteome with aging and cognitive decline: past progress and future directions. Front Aging Neurosci. 2011;23:8.Google Scholar
  39. 39.
    Lu T, Pan Y, Kao SY, et al. Gene regulation and DNA damage in the ageing human brain. Nature. 2004;429:872–81.Google Scholar
  40. 40.
    Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature. 2010;463:529–35.Google Scholar
  41. 41.
    Deak F, Sonntag WE. Aging, synaptic dysfunction, and insulin-like growth factor (IGF)-1. J Gerontol A Biol Sci Med Sci. 2012;66(6):601–25.Google Scholar
  42. 42.
    Arimatsu Y, Hatanaka H. Estrogen treatment enhances survival of cultured fetal rat amygdala neurons in a defined medium. Brain Res. 1975;390(1):151–9.Google Scholar
  43. 43.
    Seidler RD, Bo J, Anguera JA. Neurocognitive contributions to motor skill learning: the role of working memory. J Mot Behav. 2012;44(6):445–53.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Bañuelos C, LaSarge CL, McQuail JA, Hartman JJ, Gilbert RJ, Ormerod BK, Bizon JL. Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: relationship with spatial impairment. Neurobiol Aging. 2013;34(3):845–62.PubMedGoogle Scholar
  45. 45.
    Gottfries CG. Human brain levels of monoamines and their metabolites. Postmortem investigations. Acta Psychiatr Scand. 1980;61(S280):49–61.PubMedGoogle Scholar
  46. 46.
    Cowen P, Sherwood AC. The role of serotonin in cognitive function: evidence from recent studies and implications for understanding depression. J Psychopharmacol. 2013;27(7):575–83.PubMedGoogle Scholar
  47. 47.
    Seidler RD, Bernard JA, Burutolu TB, Fling BW, Gordon MT, Gwin JT, Kwak Y, Lippset DB. Motor control and aging: links to age-related brain structural, functional, and biochemical effects. Neurosci Biobehav Rev. 2010;34(5):721–33.PubMedGoogle Scholar
  48. 48.
    Mann JJ, Stanley M, Kaplan RD, Sweeney J, Neophytides A. Central catecholamine metabolism in vivo and the cognitive and motor deficits in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1983;46:905–10.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Lunenfeld B, Stratton P. The clinical consequences of an ageing world and preventive strategies. Best Pract Res Clin Obstet Gynaecol. 2014;27(5):633–49.Google Scholar
  50. 50.
    Do Rego JL, Seon JY, Burel D, Leprince J, Luu-The V, Tsutsui K, Tonon M, Pelletier G, Vaudry H. Neurosteroid biosynthesis: enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides. Front Neuroendocrinol (Elsevier Inc). 2009;30(3):259–301.Google Scholar
  51. 51.
    Compagnone NA, Mellon SH. Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol. 2000;21(1):1–56.PubMedGoogle Scholar
  52. 52.
    Crowley WR, Tessel RE, O’Donohue TL, Adler BA, Kalra SP. Effects of ovarian hormones on the concentrations of immunoreactive neuropeptide Y in discrete brain regions of the female rat: correlation with serum luteinizing hormone (LH) and median eminence LH-releasing hormone. Endocrinology (Oxford University Press). 1974;117(3):1151–5.Google Scholar
  53. 53.
    Pelletier G, Li S, Luu-The V, Labrie F. Oestrogenic regulation of pro-opiomelanocortin, neuropeptide Y and corticotrophin-releasing hormone mRNAs in mouse hypothalamus. J Neuroendocrinol (Blackwell Publishing Ltd). 2007;19(6):426–31.Google Scholar
  54. 54.
    Shimizu H, Ohtani K, Kato Y, Tanaka Y, Mori M. Estrogen increases hypothalamic neuropeptide Y (NPY) mRNA expression in ovariectomized obese rat. Neurosci Lett. 1985;204(1):80–2.Google Scholar
  55. 55.
    Thornton JE, Loose MD, Kelly MJ, Rönnekleiv OK. Effects of estrogen on the number of neurons expressing β-endorphin in the medial basal hypothalamus of the female guinea pig. J Comp Neurol (Wiley Subscription Services, Inc., A Wiley Company). 1983;341(1):67–76.Google Scholar
  56. 56.
    Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao X-B, Mobbs C, Shulman GI, Diano S, Horvath TL. Anorectic estrogen mimics leptin’s effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med. 2007;13(1):88–93.Google Scholar
  57. 57.
    Chowen JA, Torres-Alemán I, García-Segura LM. Trophic effects of estradiol on fetal rat hypothalamic neurons. Neuroendocrinology (Karger Publishers). 1981;56(6):885–90.Google Scholar
  58. 58.
    Brinto RD, Tran J, Proffitt P, Montoya M. 17β-estradiol enhances the outgrowth and survival of neocortical neurons in culture. Neurochem Res (Kluwer Academic Publishers-Plenum Publishers). 1986;22(11):1339–51.Google Scholar
  59. 59.
    Sudo S, Wen TC, Desaki J, Matsuda S, Tanaka J, Arai T, Maeda N, Sakanaka M. β-Estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil. Neurosci Res. 1986;29(4):345–54.Google Scholar
  60. 60.
    Garcia-Segura LM, Azcoitia I, DonCarlos LL. Neuroprotection by estradiol. Prog Neurobiol. 2001;62(1):29–60.Google Scholar
  61. 61.
    Scharfman HE, MacLusky NJ. Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: complexity of steroid hormone-growth factor interactions in the adult CNS. Front Neuroendocrinol. 2006;27(4):415–35.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Mendez P, Wandosell F, Garcia-Segura LM. Cross-talk between estrogen receptors and insulin-like growth factor-I receptor in the brain: cellular and molecular mechanisms. Front Neuroendocrinol. 2006;27(4):390–403.Google Scholar
  63. 63.
    Liu SB, Han J, Zhang N, Tian Z, Li XB, Zhao MG. Neuroprotective effects of oestrogen against oxidative toxicity through activation of G-protein-coupled receptor 30 receptor’. Clin Exp Pharmacol Physiol. 2011;38(9):576–84.Google Scholar
  64. 64.
    Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J Comp Neurol. 1986;387(4):507–25.Google Scholar
  65. 65.
    Ramirez VD, Zheng J. Membrane sex-steroid receptors in the brain. Front Neuroendocrinol. 1985;17(4):402–39.Google Scholar
  66. 66.
    Disshon KA, Dluzen DE. Estrogen as a neuromodulator of MPTP-induced neurotoxicity: effects upon striatal dopamine release. Brain Res. 1986;753(1–2):9–16.Google Scholar
  67. 67.
    Disshon KA, Boja JW, Dluzen DE. Inhibition of striatal dopamine transporter activity by 17beta-estradiol. Eur J Pharmacol. 1987;345(2):207–11.Google Scholar
  68. 68.
    Dluzen DE. Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. J Neurocytol (Kluwer Academic Publishers). 2000;29(5–6):386–98.Google Scholar
  69. 69.
    Bales KKR, Verina T, Cummins DJ, Du Y, Dodel RC, Saura J, Fishman CE, DeLong CA, Piccardo P, Petegnief V, Ghetti B, Paul SM. Apolipoprotein E is essential for amyloid deposition in the APPV707F transgenic mouse model of Alzheimer’s disease. Proc Natl Acad Sci. 1989;95(26):15233–8.Google Scholar
  70. 70.
    Xu H, Gouras GK, Greenfield JP, Vincen B, Naslund J, Mazzarelli L, Fried G, Jovanovic JN, Seeger M, Relkin NR, Liao F, Checler F, Buxbaum JD, Chait BT, Thinakaran G, Sisodia SS, Wang R, Greengard P, Gandy S. Estrogen reduces neuronal generation of Alzheimer bold beta-amyloid peptides. Nat Med. 1987;4(4):447–51.Google Scholar
  71. 71.
    Vegeto E, Benedusi V, Maggi A. Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases. Front Neuroendocrinol. 2008;29(4):507–19.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Vegeto E, Belcredito S, Etteri S, Ghisletti S, Brusadelli A, Meda C, Krust A, Dupont S, Ciana P, Chambon P, Maggi A. Estrogen receptor-alpha mediates the brain antiinflammatory activity of estradiol. Proc Natl Acad Sci U S A (National Academy of Sciences). 2003;99(16):9504–9.Google Scholar
  73. 73.
    Vegeto E, Belcredito S, Ghisletti S, Meda C, Etteri S, Maggi A. The endogenous estrogen status regulates microglia reactivity in animal models of neuroinflammation. Endocrinology (Oxford University Press). 2006;147(5):2262–71.Google Scholar
  74. 74.
    Garcia-Estrada J, Del Rio JA, Luquin S, Soriano E, Garcia-Segura LM. Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury. Brain Res. 1982;618(1–2):270–7.Google Scholar
  75. 75.
    Lamballe F, Smeyne RJ, Barbacid M. Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system. J Neurosci. 1983;14(1):14 LP–28.Google Scholar
  76. 76.
    Valdés JJ, Weeks OI. Estradiol and Lithium chloride specifically Alter NMDA receptor subunit NR1 mRNA and excitotoxicity in primary cultures. Brain Res. 2009;1267(May):1–12.Google Scholar
  77. 77.
    Lo DC. Chapter 7 instructive roles of neurotrophins in synaptic plasticity. Prog Brain Res. 1987;117:64–9.Google Scholar
  78. 78.
    Vicario-Abejon C, Owens D, McKay R, Segal M. Role of neurotrophins in central synapse formation and stabilization. Nat Rev Neurosci. 2002;3(12):954–74.Google Scholar
  79. 79.
    Keefe MK, Sheikh SI, Smith MG. Targeting neurotrophins to specific populations of neurons: NGF, BDNF, and NT-3 and their relevance for treatment of spinal cord injury. Int J Mol Sci. 2017;18(3):548; doi:  https://doi.org/10.3390/ijms18030548.PubMedCentralGoogle Scholar
  80. 80.
    Mitre M, Mariga A, Chao MV. Neurotrophin signalling: novel insights into mechanisms and pathophysiology. Clin Sci. 2016;131(1):13–23.Google Scholar
  81. 81.
    Cattaneo E, McKay R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature. 1979;347(6194):751–64.Google Scholar
  82. 82.
    Kuiper SD, Bramham CR. Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr Opin Drug Discov Devel. 2006;9(5):579–85.Google Scholar
  83. 83.
    Lindahl M, Saarma M, Lindholm P. Unconventional neurotrophic factors CDNF and MANF: structure, physiological functions and therapeutic potential. Neurobiol Dis (Elsevier Inc.). 2016;96:89–101.Google Scholar
  84. 84.
    Levy YS, Gilgun-Sherki Y, Melamed E, Offen D. Therapeutic potential of neurotrophic factors in neurodegenerative diseases. BioDrugs: Clin Immunotherapeutics, Biopharmaceuticals Gene Ther. 2005;19(2):96–127.Google Scholar
  85. 85.
    Connor B, Dragunow M. The role of neuronal growth factors in neurodegenerative disorders of the human brain. Brain Res Brain Res Rev. 1987;27(1):1–39.Google Scholar
  86. 86.
    Hock C, Heese K, Müller-Spahn F, Hulette C, Rosenberg C, Otten U. Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer’s disease. Neurosci Lett. 1987;241(2–3):151–4.Google Scholar
  87. 87.
    Bartus RT, Johnson EM. Clinical tests of neurotrophic factors for human neurodegenerative diseases, part 1: where have we been and what have we learned? Neurobiol Dis (Elsevier Inc.). 2015;96:156–67.Google Scholar
  88. 88.
    Bartus RT, Johnson EM. Clinical tests of neurotrophic factors for human neurodegenerative diseases, Part 2: where do we stand and where must we go next? Neurobiol Dis (Elsevier Inc.). 2016;96:168–77.Google Scholar
  89. 89.
    Bezdjian A, Kraaijenga VJC, Ramekers D, Versnel H, Thomeer HGXM, Klis SFL, Grolman W. Towards clinical application of neurotrophic factors to the auditory nerve; assessment of safety and efficacy by a systematic review of neurotrophic treatments in humans. Int J Mol Sci. 2016;17(12):1981. doi:  https://doi.org/10.3390/ijms17121981.PubMedCentralGoogle Scholar
  90. 90.
    Sonntag WE et al. Alterations in IGF-I gene and protein expression and type 1 IGF I receptors in the brains of ageing rats. Neuroscience. 1989;87.Google Scholar
  91. 91.
    Breese CR, D’Costa A, Rollins YD, Adams C, Booze RM, Sonntag WE, Leonard S. Expression of insulin‐like growth factor‐1 (IGF‐1) and IGF‐binding protein 2 (IGF‐BP2) in the hippocampus following cytotoxic lesion of the dentate gyrus. J Comp Neurol. 369(3):388–404.PubMedGoogle Scholar
  92. 92.
    Doré S, Kar S, Quirion R. Insulin-like growth factor I protects and rescues hippocampal neurons against betaamyloid- and human amylin-induced toxicity. Proc Natl Acad Sci U S A. 1986;93:4761–7.Google Scholar
  93. 93.
    Carró E, Torres-Aleman I. Serum insulin-like growth factor I in brain function. Keio J Med. 2006;55:59–62.PubMedGoogle Scholar
  94. 94.
    Knusel B, Michel PP, Schwaber JS, Hefti F. Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. Journal of Neuroscience. 1990;10(2):558–70.PubMedGoogle Scholar
  95. 95.
    Carró E, Busiguina, Torres-Aleman I. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci. 2000;20:2916–23.Google Scholar
  96. 96.
    Bellini MJ, Hereñú CB, Goya RG, Garcia-Segura LM. Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide. J Neuroinflammation. 2011;8:21.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Trejo, Carro, Garcia-Galloway, Torres-Aleman. Role of IGF-I signaling in neurodegenerative diseases. J Mol Med. 2004;81:156–61.Google Scholar
  98. 98.
    Sortino, Canonico. Neuroprotective effect of insulin-like growth factor I in immortalized hypothalamic cells. Endocrinology. 1985;137:1418–22.Google Scholar
  99. 99.
    Shavali R, Ebadi. IGF-I protects human dopaminergic SH-SY5Y cells from salsolinol induced toxicity. Neurosci Lett. 2003;340:78–81.Google Scholar
  100. 100.
    Rodriguez-Perez AI, Borrajo A, Diaz-Ruiz C, Garrido-Gil P, Labandeira-Garcia JL. Crosstalk between insulin-like growth factor-1 and angiotensin-II in dopaminergic neurons and glial cells: role in neuroinflammation and aging. Oncotarget. 2016;7:30049–67.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Hereñú CB, et al. Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction. Gene Ther. 2007;14:237–45.PubMedGoogle Scholar
  102. 102.
    Hereñú C, Sonntag W, Morel, Portiansky, Goya R. The ependymal route for IGF1 gene therapy in the brain. Neuroscience. 2009;162(1):442–7.Google Scholar
  103. 103.
    Nishida F, Morel GR, Hereñú CB, Schwerdt JI, Goya RG, Portiansky EL. Restorative effect of intracerebroventricular insulin-like growth factor-I gene therapy on motor performance in aging rats. Neuroscience. 2011;176:194–206.Google Scholar
  104. 104.
    Mainardi M, Fusco S, Grassi C. Modulation of hippocampal neural plasticity by glucose-related signaling. Neural Plast. 2015;2015:657928.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Liquitaya-Montiel A, Aguilar-Arredondo A, Arias C, Zepeda A. Insulin growth factor-I promotes functional recovery after a focal lesion in the dentate gyrus. CNS Neurol Disord Drug Targets. 2012;11(7):808–28.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Macarena Lorena Herrera
    • 1
  • Eugenia Falomir-Lockhart
    • 2
  • Franco Juan Cruz Dolcetti
    • 2
  • Nathalie Arnal
    • 2
  • María José Bellini
    • 2
  • Claudia Beatriz Hereñú
    • 1
    Email author
  1. 1.Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Farmacología, Córdoba, Argentina, Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET)Ciudad UniversitariaCórdobaArgentina
  2. 2.Universidad Nacional de La Plata, Facultad de Ciencias Médicas, Buenos Aires, Argentina. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP-CONICET)Buenos AiresArgentina

Personalised recommendations