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Insulin-like Growth Factor I: Regulation and Interactions During Aging-Induced Cognitive Decline and Impairment Within the Hippocampus

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IGFs in the Nervous System

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Abstract

A considerable body of evidence indicates that hippocampal circuitry is especially vulnerable to the neurodegeneration associated with normal and pathological aging. However, aged hippocampus appears to retain some of its capacity to regenerate in response to this damage [1–3]. Axonal sprouting and synaptic reorganization have been reported in hippocampal regions sustaining loss of cells or input during normal aging [2, 3]. Neurotrophic factors (NTFs) are believed to be necessary for such structural reorganization. One family of NTFs, the insulin-like growth factors (IGFs), may have actions on a broad spectrum of hippocampal cells [4–10]. This family of growth factors consists of two peptides, IGF-I and IGF-1I, which interact with two different receptors, the type 1 and type 2 IGF receptors (IGFR). The type 1 IGFR, which has high affinity for both IGFs, mediates many of the proliferative and differentiative actions of the IGFs [9, 10]. The functional role of the type 2 receptor, which has high affinity for IGF-II but low affinity for IGF-I, is not well defined [11–14]. The IGF system also includes a family of six IGF binding proteins (IGFBPs) that modulate IGF action and availability in tissue-, cell-, and development-specific manners [9,10].

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References

  1. Hefti F (1994) Neurotrophic factor therapy for nervous system degenerative diseases. J Neurobiol 25: 1418–1435

    Article  PubMed  CAS  Google Scholar 

  2. Flood DG, Coleman PD (1988) Neuron numbers and sizes in aging brain: comparison of human, monkey, and rodent brain. Neurobiol Aging 9: 453–463

    Article  PubMed  CAS  Google Scholar 

  3. Flood DG, Coleman PD (1990) Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer’s disease. Prog Brain Res 83: 453–443

    Google Scholar 

  4. Beck KD, Powell-Braxton L, Widmer H-R, Valverde J, Hefti F (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

    Google Scholar 

  5. Bondy CA, Werner H, Roberts CT Jr, LeRoith D (1992) Cellular pattern of type 1 insulin-like growth factor receptor gene expression during maturation of the rat brain: Comparison with insulin-like growth factors I and II. Neuroscience 46: 909–923

    Google Scholar 

  6. Couce ME, Weatherington AJ, McGinty JF (1992) Expression of insulin-like growth factor-II (IGF-II) and IGF-II/mannose-6-phosphate receptor in the rat hippocampus: an in situ hybridization and immunocytochemical study. Endocrinology 131: 1636–1642

    Google Scholar 

  7. Kar S, Baccichet A, Quirion R, Poirier J (1993) Entorhinal cortex lesion induces differential responses in [125I] insulin-like growth factor I, [125I] insulin-like growth factor II, and [125I] insulin receptor binding sites in the rat hippocampal formation. Neuroscience 55: 69–80

    Article  PubMed  CAS  Google Scholar 

  8. Stenvers KL, Zimmermann EM, Gallagher M, Lund PK (1994) Expression of insulinlike growth factor binding protein-4 and -5 mRNAs in adult rat forebrain. J Comp Neurol 339: 91–105

    Article  PubMed  CAS  Google Scholar 

  9. Hepler JE, Lund PK (1990) Molecular biology of the insulin-like growth factors: relevance to nervous system function. Mol Neurobiol 2: 93–127

    Article  Google Scholar 

  10. D’Ercole AJ, Ping Y, Calikoghi AS, Ospiana GG (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13: 227–255

    Article  PubMed  Google Scholar 

  11. Bondy C (1991) Transient IGF I gene expression during maturation of functionally related central projection neurons. J Neurosci 11: 3442–3455

    PubMed  CAS  Google Scholar 

  12. Brar AK, Chernausek SD (1993) Localization of insulin-like growth factor binding protein-4 expression in the developing and adult rat brain: analysis by in situ hybridization. J Neurosci Res 35: 103–114

    Article  PubMed  CAS  Google Scholar 

  13. Reinhardt RR, Bondy CA (1994) Insulin-like growth factors cross the blood brain barrier. Endocrinology 135: 1753–1761

    Article  PubMed  CAS  Google Scholar 

  14. Gluckman PD, Guan J, Beiharz EJ, Klempt ND, Klempt M, Miller O, Sirimanne E, Dragunow M, Williams CE (1993) The role of the insulin-like growth factor system in neuronal rescue. Ann N Y Acad Sci 692: 138–148

    Article  PubMed  CAS  Google Scholar 

  15. Guthrie KM, Nguyen T, Gall CM (1995) Insulin-like growth factor-1 mRNA is increased in deafferented hippocampus: spatiotemporal correspondence of a trophic event with axon sprouting. J Comp Neurol 352: 147–160

    Article  PubMed  CAS  Google Scholar 

  16. Kitraki E, Bozas E, Philippidis H, Stylianopoulou F (1993) Aging-related changes in IGF-II and c-fos gene expression in the rat brain. Int J Dev Neurosci 11: 1–9

    Article  PubMed  CAS  Google Scholar 

  17. Park GH, Buetow DE (1991) Genes for insulin-like growth factors I and II are expressed in senescent rat tissues. Gerontology 37: 310–316

    Article  PubMed  CAS  Google Scholar 

  18. Stenvers KL, Lund PK, Gallagher M (1996) Increased expression of type 1 insulin-like growth factor receptor messenger RNA in rat hippocampal formation is associated with aging and behavioral impairment. Neuroscience 72: 505–518

    Article  PubMed  CAS  Google Scholar 

  19. Gallagher M, Gill TM, Baxter MG, Bucci DJ (1994) The development of neurobiological models for cognitive decline in aging. Semin Neurosci 6: 351–358

    Article  Google Scholar 

  20. Gallagher M, Burwell R, Burchinal M (1993) Severity of spatial learning impairment in aging: development of a learning index score for performance in the Morris water maze. Behav Neurosci 107: 618–626

    Article  PubMed  CAS  Google Scholar 

  21. Bando H, Zhang C, Takada Y, Yamasaki R, Saito S (1991) Impaired secretion of growth hormone-releasing hormone, growth hormone, and IGF-I in elderly men. Acta Endo Copenh 124: 31–36

    CAS  Google Scholar 

  22. D’Costa A, Lenham JE, Ingram RL, Sonntag WE (1993) Comparison of protein synthesis in brain and peripheral tissue during aging. Relationship to insulin-like growth factor-1 and type 1 IGF receptors. Ann N Y Acad Sci 692: 253–255

    Article  PubMed  Google Scholar 

  23. Haselbacher G, Humbel R (1982) Evidence for two species of insulin-like growth factor II (IGF II and big IGF II) in human spinal fluid. Endocrinology 110: 1822–1824

    Google Scholar 

  24. Barnes CA (1994) Normal aging: regional specific changes in hippocampal synaptic transmission. Trends Neurosci 17: 13–18

    Article  PubMed  CAS  Google Scholar 

  25. Nitsch R (1993) Transneuronal changes in the lesioned entorhinal-hippocampal system. Hippocampus 3: 247–256

    Article  PubMed  Google Scholar 

  26. Lapchak PA, Jenden DJ, Hefti F (1991) Compensatory elevation of acetylcholine synthesis in vivo by cholinergic neurons surviving partial lesions of septohippocampal pathway. J Neurosci 12: 4737–4744

    Google Scholar 

  27. Stenvers K, Lund PK, Gallagher M (1997) Two deafferenting lesions of the hippocampus produce differential changes in IGF mRNA expression in rats. J Neurosci (submitted)

    Google Scholar 

  28. Baxter MG, Bucci DJ, Wiley RG, Gorman LK, Gallagher M (1995) Selective immuno- toxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats. Behav Neurosci 109: 714–722

    Article  PubMed  CAS  Google Scholar 

  29. Amaral DG, Witter MP (1995) Hippocampal formation. In: Paxinos G (ed) The rat nervous system. Academic Press, New York, pp 443–493

    Google Scholar 

  30. Lund PK (1994) Insulin-like growth factors. In: Dockray G, Walsh JH (eds) Gut peptides: Biochemistry and physiology. Raven, New York, pp 587–613

    Google Scholar 

  31. Simmons JG, Hoyt EC, Westwick JK, Brenner DA, Pucilowska JB, Lund PK (1995) Insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) interact to regulate growth and gene expression in IEC-6 intestinal epithelial cells. Mol Endocrinol 9: 1157–1165

    Article  PubMed  CAS  Google Scholar 

  32. Merlo GR, Basolo F, Fiore L, Duboc L, Hynes NE (1995) p53-dependent and p53-independent activation of apoptosis in mammary epithelial cells reveal a survival function of EGF and insulin. J Cell Biol 128: 1185–1196

    Google Scholar 

  33. Lund PK, Zimmerman EM (1996) Insulin-like growth factors and inflammatory disease. In: Goodlaerd R, Wright N (eds) Cytokines and growth factors in gastroenterology. Bailliere’s Clin Gastroenterol, vol 10, London, pp 83–96

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Physiology and Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina, USA

    P. K. Lund

  2. Ludwig Institute for Cancer Research, Melbourne, Australia

    K. L. Stenvers

  3. Department of Psychology, Johns Hopkins University, Baltimore, Maryland, USA

    M. Gallagher

Authors
  1. P. K. Lund
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  2. K. L. Stenvers
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  3. M. Gallagher
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Editor information

Editors and Affiliations

  1. Department of Medical Pharmacology, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy

    Eugenio E. Müller

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© 1998 Springer-Verlag Italia, Milano

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Lund, P.K., Stenvers, K.L., Gallagher, M. (1998). Insulin-like Growth Factor I: Regulation and Interactions During Aging-Induced Cognitive Decline and Impairment Within the Hippocampus. In: Müller, E.E. (eds) IGFs in the Nervous System. Springer, Milano. https://doi.org/10.1007/978-88-470-2246-1_4

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  • DOI: https://doi.org/10.1007/978-88-470-2246-1_4

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-3-540-75042-0

  • Online ISBN: 978-88-470-2246-1

  • eBook Packages: Springer Book Archive

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