Skip to main content
SpringerLink
Log in

Glial-neurotrophic mechanisms in Down syndrome

  • Chapter
Protein Expression in Down Syndrome Brain

Summary

Complex interactions and interconnectivity between neurons are hallmarks of normal neuronal differentiation and development. Neurons also interact with other cell types, notably glia, and rely on substances released by glia for their normal function. A deficit in glial response may disturb this critical neuronal-glial-neuronal interaction in Down syndrome (DS), leading to loss of neurons and other defects of development, and contribute to cognitive limitation and early onset of Alzheimer disease.

The hypothesis this paper will discuss is that normal neural development involves an activity-dependent release of substances from neurons, and that these substances act upon glia cells which in turn release substances that influence neurons to promote their survival and development. This glial influence affects cortical neurons and also the subcortical cholinergic neurons that project to the cerebral and hippocampal cortices to maintain cortical neuronal excitability and activity. The neuronal activity stimulates glial secretion of sustaining substances, in a reciprocally interactive cycle. Some aspect of this “virtuous cycle” is deficient in Down syndrome. The result is a small but slowly increasing deficit in activity-dependent support by glia cells which produces a gradually increasing abnormality of cortical and subcortical, perhaps especially cholinergic, function.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ades AM, McCune SK, Crnic LS, Ring M, Brenneman DE, HiLL JM (2000) Vasoactive intestinal peptide dysfunction associated with a segmental trisomy model of Down syndrome [Abstract]. Soc Ped Res 79: 472

    Google Scholar 

  • Bambrick LL, Golovina VA, Blaustein MP, Yarowsky PJ, Krueger BK (1997) Abnormal calcium homeostasis in astrocytes from the trisomy 16 mouse. Glia 19: 352–358

    Article  PubMed  CAS  Google Scholar 

  • Bear MF, Singer W (1986) Modulation of visual cortical plasticity by acetylcholine and noradrenaline. Nature 320: 172–176

    Article  PubMed  CAS  Google Scholar 

  • Blondel O, Collin C, McCarran B, Zhu X, Zamostiano R, Gozes I, Brenneman DE, McKay R (2000) A glia-derived signal regulating neuronal differentiation. J Neurosci 20: 8012–8020

    PubMed  CAS  Google Scholar 

  • Brenneman DE (1986) Role of electrical activity and trophic factors during cholinergic development in dissociated cultures. Can J Physiol Pharmacol 64: 356–362

    Article  PubMed  CAS  Google Scholar 

  • Brenneman DE, Yu C, Nelson PG (1990) Multi-determinate regulation of neuronal survival: neuropeptides, excitatory amino acids and bioelectric activity. Int J Dev Neurosci 8: 371–378

    Article  PubMed  CAS  Google Scholar 

  • Brenneman DE, Hill JM, Glazner GW, Gozes I, Phillips TM (1995) Interleukin-1 alpha and vasoactive intestinal peptide: enigmatic regulation of neuronal survival. Int J Dew Neurosci 13: 187–200

    Article  CAS  Google Scholar 

  • Brenneman DE, Westbrook GL, Fitzgerald SP, Ennist DL, Elkins KL, Ruff MR, Pert CB (1998) Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature 335: 639–642

    Article  Google Scholar 

  • Brenneman DE, Hauser J, Phillips TM, Davidson A, Bassan M, Gozes I (1999) Vasoactive intestinal peptide: link between electrical activity and glia mediated neurotrophism. Ann NY Acad Sci 897: 17–26

    Article  PubMed  CAS  Google Scholar 

  • Brown R (2000) Neuronal release of vasoactive intestinal peptide is important to astrocyte protection of neurons from glutamate toxicity. Mol Cell Neurosci 15: 465–475

    Article  PubMed  CAS  Google Scholar 

  • Caserta MT (1994) Neuropeptide Y immunoreactive neurons in murine trisomy 16 cortical cultures. Plasticity of expression and differentiation Mol. Chem Neuropathol 22: 197–210

    Article  CAS  Google Scholar 

  • Davisson MT, Schmidt C, Reeves RH, Irving NG, Akeson EC, Harris BS, Bronson RT (1993) Segmental trisomy as a mouse model for Down syndrome. Prog Clin Biol Res 384: 117–133

    PubMed  CAS  Google Scholar 

  • de la Monte SM (1999) Molecular abnormalities of the brain in Down syndrome, relevance to Alzheimer’s neurodegeneration. J Neural Transm [Suppl] 57: 1–19

    Google Scholar 

  • Delcroix JD, Cooper JD, Howe CL, Belichenko PV, Valleta JS, Lee AAT, Mobley WC (1999) Failure of axonal retrograde 1251-NGF transport by septal neurons in a mouse model of Down syndrome. J Neurosci 19: 523–527

    Google Scholar 

  • Ford KA, Granholm ARE, Crnic LS, Hyde LA, Seo H, Ferree AW, Isacson O (2000) Alterations in APP and NGF levels in an animal model of Down syndrome. Neurosci Abstr 76: 421

    Google Scholar 

  • Glazner G, Gressens P, Lee SJ, Gibney G, Gozes I, Gozes Y, Brenneman DE, Hill JM(1999) Activity-dependent neurotrophic factor: a potent regulator of embryonic growth and development. Anat Embryol 200: 65–71

    Article  PubMed  CAS  Google Scholar 

  • Gomariz RP, Martinez C, Abad C, Leceta J, Delgado M (2001) Immunology of VIP: a review and theapeutical perspectives. Curr Pharm Des 7: 89–111

    Article  PubMed  CAS  Google Scholar 

  • Gozes I, Bardea A, Reshef A, Zamostiano R, Zhukovsky S, Rubinraut S, Fridkin M,Brenneman DE (1996) Neuroprotective strategy for Alzheimer disease: intranasal administration of a fatty neuropeptide. Proc Natl Acad Sci 93: 427–432

    Article  PubMed  CAS  Google Scholar 

  • Gozes I, Bachar M, Bardea A, Davidson A, Rubinraut S, Fridkin M, Giladi E (1997) Protection against developmental retardation in apolipoprotein E deficient mice by a fatty neuropeptide: implications for early treatment of Alzheimer’s disease. J Neurobiol 33: 329–342

    Article  PubMed  CAS  Google Scholar 

  • Gozes I, Bassan M, Zamostiano R, Pinhasov A, Davidson A, Giladi E et al. (1999) A novel signaling molecule for neuropeptide action: activity-dependent neuroprotective protein. Ann NY Acad Sci 897: 125–135

    Article  PubMed  CAS  Google Scholar 

  • Granholm ARE, Sanders LA, Crnic LS (2000) Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down syndrome. Exp Neurol 161: 647–663

    Article  PubMed  CAS  Google Scholar 

  • Gressens P, Marret S, Hill JM, Brenneman DE, Gozes I, Fridkin M, Evrard P (1997) Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain. J Clin Invest 100: 390–397

    Article  PubMed  CAS  Google Scholar 

  • Griffin WS, Sheng JG, Royston MC, Gentleman SM, McKenzie JE, Graham DI, Roberts GW, Mark RE (1998) Glial-neuronl Interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 8: 65–72

    Article  PubMed  CAS  Google Scholar 

  • Gu Q, Singer W (1989) The role of muscarinic receptors in ocular dominance plasticity. EXS 57: 305–314

    PubMed  CAS  Google Scholar 

  • Hohmann CF, Berger-Sweeney J (1998) Cholinergic regulation of cortical development and plasticity, new twists to an old story. Persp Dev Neurobiol 5: 401–425

    CAS  Google Scholar 

  • Holtzman DM, Kilbridge J, Chen K, Rabin J, Luche R, Carlson E, Epstein CJ, Mobley WC (1995) Preliminary characterization of the central nervous system in partial trisomy 16 mice. Prog Clin Biol Res 393: 227–240

    PubMed  CAS  Google Scholar 

  • Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K, Sun Y, Carlson E, Alleva E, Epstein CJ, Mobley WC (1996) Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci 93: 13333–13338

    Article  PubMed  CAS  Google Scholar 

  • Insausti AM, Megias M, Crespo D, Cruz-Orive LM, Dierssen M, Vallina TF, Insausti R, Florez J (1998) Hippocampal volume and neuronal number in mice: a murine model of Down syndrome. Neurosci Lett 253: 175–178

    Article  PubMed  CAS  Google Scholar 

  • Kalfin R, Maulik N, Engelman RM, Cordis GA, Milenov K, Kasakov L, Das DK (1994) Protective role of intracoronary vasoactive intestinal peptide in ischemic and reperfused myocardium. J Pharmacol Exp Ther 268: 953–958

    Google Scholar 

  • Korsching S, Thoenen H (1983) Quantitative demonstration of the retrograde axonal transport of endogenous nerve growth factor, Neurosci Lett 39: 1–4

    Article  PubMed  CAS  Google Scholar 

  • Krnjevic K, Pumain R, Renaud L (1971) The mechanism of execitation by acetylcholine in the cerebral cortex. J Physiol 215: 247–268

    PubMed  CAS  Google Scholar 

  • Martinez C, Delgado M, Abad C, Gomariz RP, Ganea D, Leceta J (1999) Regulation of VIP production and secretion by murine lymphocytes. J Neuroimmunol 93: 126–138

    Article  PubMed  CAS  Google Scholar 

  • Muller W, Heinemann U, Schuchmann S (1997) Impaired Ca-signaling in astrocytes from the Tsl6 mouse model of Down syndrome. Neurosci Lett 223: 81–84

    Article  PubMed  CAS  Google Scholar 

  • Nelson KB, Grether JK, Croen LA, Dambrosia JM, Dickens BF, Jelliffe LL, Hansen RL, Phillips TM (2001) Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol 49: 597–606

    Article  PubMed  CAS  Google Scholar 

  • Nelson PG, Fitzgerald S, Rapoport SI, Neale EA, Galdzicki Z, Dunlap V, Bowers L, van Agoston (1997) Cerrebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture. Proc Natl Acad Sci 94: 12644–12648

    Article  PubMed  CAS  Google Scholar 

  • Pitts RL, Wang S, Jones EA, Symes AJ (2001) Transforming growth factor beta and ciliary neurotrophic factor synergisticlly induce vasoactive intestinal peptide gene expression through the cooperation of Smad, Stat and AP-1 sites. J Biol Chem (Epublication ahead of print)

    Google Scholar 

  • Richtsmeier JT, Baxter LL, Reeves RH (2000) Parallels of craniofacial caldevelopment in Down syndrome and Ts65Dn mice. Dev Dynam 17: 137–145

    Article  Google Scholar 

  • Schwartz JP, Mishler K (1990) Beta-adrenergic receptor regulation, through cyclic AMP, of nerve growth factor expression in rat cortical and cerebellar strocytes. Cell Mol Neurobiol 10: 447–457

    Article  PubMed  CAS  Google Scholar 

  • Seiler M, Schwab ME (1984) Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Res 300: 33–39

    Article  PubMed  CAS  Google Scholar 

  • Spong C, Abebe DT, Gozes I, Brenneman DE, Hill JM (2001) Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. J Pharmacol Exp Ther 297: 774–779

    PubMed  CAS  Google Scholar 

  • Symes AJ, Pitts RL, Conover J, Kos K, Coulombre J (2000) Synergy of activin and ciliary neurotrophic factor signaling pathways in the induction of vasoactive intestinal peptide gene expression. Mol Endocrinol 14: 429–439

    Article  PubMed  CAS  Google Scholar 

  • Ure DR, Campenot RB (1994) Leukemia inhibitory factor and nerve growth factor are retrogratedly transported and processed by cultured rat sympathetic neurons. Dev Biol 162: 339–347

    Article  PubMed  CAS  Google Scholar 

  • Wang S, Rosengren LE, Franlund M, Hamberger A, Haglid KG (1999) Bcl 2 expression regulates cell sensitivity to S100-b mediated apoptosis. Brain Res Mol Brain Res 0: 167–176

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, Bethesda, MD, USA

    P. G. Nelson

  2. Department of Neonatology, Children’s National Medical Center, Washington, DC, USA

    S. K. McCune & A. M. Ades

  3. Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA

    K. B. Nelson

Authors
  1. P. G. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. K. McCune
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. M. Ades
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. B. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Universität-Kinderklinik, Währinger Gürtel 18-20, A-1090, Wien, Austria

    Gert Lubec

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer-Verlag/Wien

About this chapter

Cite this chapter

Nelson, P.G., McCune, S.K., Ades, A.M., Nelson, K.B. (2001). Glial-neurotrophic mechanisms in Down syndrome. In: Lubec, G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6262-0_7

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83704-7

  • Online ISBN: 978-3-7091-6262-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation