Skip to main content

Advertisement

SpringerLink
Log in

NCAM Function in the Adult Brain: Lessons from Mimetic Peptides and Therapeutic Potential

  • Overview
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Neural cell adhesion molecules (NCAMs) are complexes of transmembranal proteins critical for cell–cell interactions. Initially recognized as key players in the orchestration of developmental processes involving cell migration, cell survival, axon guidance, and synaptic targeting, they have been shown to retain these functions in the mature adult brain, in relation to plastic processes and cognitive abilities. NCAMs are able to interact among themselves (homophilic binding) as well as with other molecules (heterophilic binding). Furthermore, they are the sole molecule of the central nervous system undergoing polysialylation. Most interestingly polysialylated and non-polysialylated NCAMs display opposite properties. The precise contributions each of these characteristics brings in the regulations of synaptic and cellular plasticity in relation to cognitive processes in the adult brain are not yet fully understood. With the aim of deciphering the specific involvement of each interaction, recent developments led to the generation of NCAM mimetic peptides that recapitulate identified binding properties of NCAM. The present review focuses on the information such advances have provided in the understanding of NCAM contribution to cognitive function.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Edelman GM, Cunningham BA (1990) Place-dependent cell adhesion, process retraction, and spatial signaling in neural morphogenesis. Cold Spring Harb Symp Quant Biol 55:303–318

    Article  PubMed  CAS  Google Scholar 

  2. Edelman GM (1986) Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu Rev Cell Biol 2:81–116

    Article  PubMed  CAS  Google Scholar 

  3. Nybroe O, Bock E (1990) Structure and function of the neural cell adhesion molecules NCAM and L1. Adv Exp Med Biol 265:185–196

    PubMed  CAS  Google Scholar 

  4. Rønn LC, Bock E, Linnemann D, Jahnsen H (1995) NCAM-antibodies modulate induction of long-term potentiation in rat hippocampal CA1. Brain Res 677:145–151

    Article  PubMed  Google Scholar 

  5. Lüthi A, Mohajeri H, Schachner M, Laurent JP (1996) Reduction of hippocampal long-term potentiation in transgenic mice ectopically expressing the neural cell adhesion molecule L1 in astrocytes. J Neurosci Res 46:1–6

    Article  PubMed  Google Scholar 

  6. Tessier-Lavigne M, Goodman CS (1996) The molecular biology of axon guidance. Science (New York, NY) 274:1123–1133

    Article  CAS  Google Scholar 

  7. Gascon E, Vutskits L, Kiss JZ (2010) The role of PSA-NCAM in adult neurogenesis. Adv Exp Med Biol 663:127–136

    Article  PubMed  CAS  Google Scholar 

  8. Kasper C, Rasmussen H, Kastrup JS, Ikemizu S, Jones EY et al (2000) Structural basis of cell–cell adhesion by NCAM. Nat Struct Biol 7:389–393

    Article  PubMed  CAS  Google Scholar 

  9. Soroka V, Kolkova K, Kastrup JS, Diederichs K, Breed J et al (1993) (2003) Structure and interactions of NCAM Ig1-2-3 suggest a novel zipper mechanism for homophilic adhesion. Structure (London, England: 1993) 11:1291–1301

    Article  CAS  Google Scholar 

  10. Walmod PS, Kolkova K, Berezin V, Bock E (2004) Zippers make signals: NCAM-mediated molecular interactions and signal transduction. Neurochem Res 29:2015–2035

    Article  PubMed  CAS  Google Scholar 

  11. Horstkorte R, Schachner M, Magyar JP, Vorherr T, Schmitz B (1993) The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth. J Cell Biol 121:1409–1421

    Article  PubMed  CAS  Google Scholar 

  12. Brümmendorf T, Rathjen FG (1996) Structure/function relationships of axon-associated adhesion receptors of the immunoglobulin superfamily. Curr Opin Neurobiol 6:584–593

    Article  PubMed  Google Scholar 

  13. Kiselyov VV, Skladchikova G, Hinsby AM, Jensen PH, Kulahin N et al (2003) Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure (London, England 1993) 11:691–701

    Article  CAS  Google Scholar 

  14. Doherty P, Walsh F (1996) CAM-FGF receptor interactions: a model for axonal growth. Mol Cell Neurosci 8:99–111

    Article  CAS  Google Scholar 

  15. Kiselyov V V (2008) NCAM and the FGF-Receptor. Neurochemical research

  16. Rutishauser U, Landmesser L (1996) Polysialic acid in the vertebrate nervous system: a promoter of plasticity in cell–cell interactions. Trends Neurosci 19:422–427

    PubMed  CAS  Google Scholar 

  17. Rønn LC, Olsen M, Ostergaard S, Kiselyov V, Berezin V et al (1999) Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides. Nat Biotechnol 17:1000–1005

    Article  PubMed  Google Scholar 

  18. Rønn LCB, Olsen M, Soroka V, ØStergaard S, Dissing S et al (2002) Characterization of a novel NCAM ligand with a stimulatory effect on neurite outgrowth identified by screening a combinatorial peptide library. Eur J Neurosci 16:1720–1730

    Article  PubMed  Google Scholar 

  19. Soroka V, Kiryushko D, Novitskaya V, Ronn LCB, Poulsen FM et al (2002) Induction of neuronal differentiation by a peptide corresponding to the homophilic binding site of the second Ig module of the neural cell adhesion molecule. J Biol Chem 277:24676–24683

    Article  PubMed  CAS  Google Scholar 

  20. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  21. Cooke SF, Bliss TVP (2006) Plasticity in the human central nervous system. Brain: J Neurol 129:1659–1673

    Article  CAS  Google Scholar 

  22. Lüthl A, Laurent JP, Figurov A, Muller D, Schachner M (1994) Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM. Nature 372:777–779

    Article  PubMed  Google Scholar 

  23. Muller D, Wang C, Skibo G, Toni N, Cremer H et al (1996) PSA-NCAM is required for activity-induced synaptic plasticity. Neuron 17:413–422

    Article  PubMed  CAS  Google Scholar 

  24. Stoenica L, Senkov O, Gerardy-Schahn R, Weinhold B, Schachner M et al (2006) In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion molecule NCAM or its polysialic acid. Eur J Neurosci 23:2255–2264

    Article  PubMed  Google Scholar 

  25. Bukalo O, Fentrop N, Lee AYW, Salmen B, Law JWS et al (2004) Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus. J Neurosci: Off J Soc Neurosci 24:1565–1577

    Article  CAS  Google Scholar 

  26. Becker CG, Artola A, Gerardy-Schahn R, Becker T, Welzl H et al (1996) The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation. J Neurosci Res 45:143–152

    Article  PubMed  CAS  Google Scholar 

  27. Eckhardt M, Bukalo O, Chazal G, Wang L, Goridis C et al (2000) Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination of the roles of neural cell adhesion molecule protein and polysialic acid in neural development and synaptic plasticity. J Neurosci: Off J Soc Neurosci 20:5234–5244

    CAS  Google Scholar 

  28. Dityatev A, Dityateva G, Sytnyk V, Delling M, Toni N et al (2004) Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci: Off J Soc Neurosci 24:9372–9382

    Article  CAS  Google Scholar 

  29. Rodríguez JJ, Dallérac GM, Tabuchi M, Davies HA, Colyer FM et al (2008) N-methyl-D-aspartate receptor independent changes in expression of polysialic acid-neural cell adhesion molecule despite blockade of homosynaptic long-term potentiation and heterosynaptic long-term depression in the awake freely behaving rat dentate gyrus. Neuron glia Biol 4:169–178

    Article  PubMed  Google Scholar 

  30. Guiraudie-Capraz G, Chaillan FA, Truchet B, Franc JL, Mourre C et al (2011) Increase in polysialyltransferase gene expression following LTP in adult rat dentate gyrus. Hippocampus 21:1180–1189

    Article  PubMed  CAS  Google Scholar 

  31. Yang P, Major D, Rutishauser U (1994) Role of charge and hydration in effects of polysialic acid on molecular interactions on and between cell membranes. J Biol Chem 269:23039–23044

    PubMed  CAS  Google Scholar 

  32. Johnson CP, Fujimoto I, Rutishauser U, Leckband DE (2005) Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion. J Biol Chem 280:137–145

    PubMed  CAS  Google Scholar 

  33. Køhler LB, Soroka V, Korshunova I, Berezin V, Bock E (2010) A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival. J Neurosci Res 88:2165–2176

    Article  PubMed  CAS  Google Scholar 

  34. Kraev I, Henneberger C, Rossetti C, Conboy L, Kohler LB et al (2011) A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus. PLoS ONE 6:e23433

    Article  PubMed  CAS  Google Scholar 

  35. Kiryushko D, Kofoed T, Skladchikova G, Holm A, Berezin V et al (2003) A synthetic peptide ligand of neural cell adhesion molecule (NCAM), C3d, promotes neuritogenesis and synaptogenesis and modulates presynaptic function in primary cultures of rat hippocampal neurons. J Biol Chem 278:12325–12334

    Article  PubMed  CAS  Google Scholar 

  36. Cambon K, Hansen SM, Venero C, Herrero a I, Skibo G et al (2004) A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosc: Off J Soc Neurosci 24:4197–4204

    Article  CAS  Google Scholar 

  37. Hansen SMM, Køhler LB, Li S, Kiselyov V, Christensen C et al (2008) NCAM-derived peptides function as agonists for the fibroblast growth factor receptor. J Neurochem 106:2030–2041

    PubMed  CAS  Google Scholar 

  38. Dallérac G, Zerwas M, Novikova T, Callu D, Leblanc-Veyrac P et al (2011) The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo. Learn Memory (Cold Spring Harbor, NY) 18:306–313

    Article  CAS  Google Scholar 

  39. Knafo S, Venero C, Sánchez-Puelles C, Pereda-Peréz I, Franco A et al (2012) Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement. PLoS Biol 10:e1001262

    Article  PubMed  CAS  Google Scholar 

  40. Downer EJ, Cowley TR, Lyons A, Mills KHG, Berezin V et al (2010) A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL. Neurobiol Aging 31:118–128

    Article  PubMed  CAS  Google Scholar 

  41. Archer FR, Doherty P, Collins D, Bolsover SR (1999) CAMs and FGF cause a local submembrane calcium signal promoting axon outgrowth without a rise in bulk calcium concentration. Eur J Neurosci 11:3565–3573

    Article  PubMed  CAS  Google Scholar 

  42. Rosenthal R, Malek G, Salomon N, Peill-Meininghaus M, Coeppicus L et al (2005) The fibroblast growth factor receptors, FGFR-1 and FGFR-2, mediate two independent signalling pathways in human retinal pigment epithelial cells. Biochem Biophys Res Commun 337:241–247

    Article  PubMed  CAS  Google Scholar 

  43. Kiryushko D, Korshunova I, Berezin V, Bock E (2006) Neural cell adhesion molecule induces intracellular signaling via multiple mechanisms of Ca 2 Homeostasis. Mol Biol Cell 17:2278–2286

    Article  PubMed  CAS  Google Scholar 

  44. Tang J, Rutishauser U, Landmesser L (1994) Polysialic acid regulates growth cone behavior during sorting of motor axons in the plexus region. Neuron 13:405–414

    Article  PubMed  CAS  Google Scholar 

  45. Tang J, Landmesser L, Rutishauser U (1992) Polysialic acid influences specific pathfinding by avian motoneurons. Neuron 8:1031–1044

    Article  PubMed  CAS  Google Scholar 

  46. Weinhold B, Seidenfaden R, Röckle I, Mühlenhoff M, Schertzinger F et al (2005) Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule. J Biol Chem 280:42971–42977

    Article  PubMed  CAS  Google Scholar 

  47. Bonfanti L, Olive S, Poulain DA, Theodosis DT (1992) Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study. Neuroscience 49:419–436

    Article  PubMed  CAS  Google Scholar 

  48. Miller PD, Styren SD, Lagenaur CF, DeKosky ST (1994) Embryonic neural cell adhesion molecule (N-CAM) is elevated in the denervated rat dentate gyrus. J Neurosci: Off J Soc Neurosci 14:4217–4225

    CAS  Google Scholar 

  49. Theodosis DT, Rougon G, Poulain DA (1991) Retention of embryonic features by an adult neuronal system capable of plasticity: polysialylated neural cell adhesion molecule in the hypothalamo-neurohypophysial system. Proc Natl Acad Sci USA 88:5494–5498

    Article  PubMed  CAS  Google Scholar 

  50. Theodosis DT, Bonhomme R, Vitiello S, Rougon G, Poulain a D (1999) Cell surface expression of polysialic acid on NCAM is a prerequisite for activity-dependent morphological neuronal and glial plasticity. J Neurosci: Off J Soc Neurosci 19:10228–10236

    CAS  Google Scholar 

  51. Hoyk Z, Parducz A, Theodosis DT (2001) The highly sialylated isoform of the neural cell adhesion molecule is required for estradiol-induced morphological synaptic plasticity in the adult arcuate nucleus. Eur J Neurosci 13:649–656

    Article  PubMed  CAS  Google Scholar 

  52. Kiselyov VV, Berezin V, Maar TE, Soroka V, Edvardsen K et al (1997) The first immunoglobulin-like neural cell adhesion molecule (NCAM) domain is involved in double-reciprocal interaction with the second immunoglobulin-like NCAM domain and in heparin binding. J Biol Chem 272:10125–10134

    Article  PubMed  CAS  Google Scholar 

  53. Pedersen MV, Køhler LB, Ditlevsen DK, Li S, Li S et al (2004) Neuritogenic and survival-promoting effects of the P2 peptide derived from a homophilic binding site in the neural cell adhesion molecule. J Neurosci Res 75:55–65

    Article  PubMed  CAS  Google Scholar 

  54. Li S, Kolkova K, Rudenko O, Soroka V, Poulsen FM et al (2005) Triple effect of mimetic peptides interfering with neural cell adhesion molecule homophilic cis interactions. Biochemistry 44:5034–5040

    Article  PubMed  CAS  Google Scholar 

  55. Kiselyov VV, Soroka V, Berezin V, Bock E (2005) Structural biology of NCAM homophilic binding and activation of FGFR. J Neurochem 94:1169–1179

    Article  PubMed  CAS  Google Scholar 

  56. Jacobsen J, Kiselyov V, Bock E, Berezin V (2008) A peptide motif from the second fibronectin module of the neural cell adhesion molecule, NCAM, NLIKQDDGGSPIRHY, is a binding site for the FGF receptor. Neurochem Res 33:2532–2539

    Article  PubMed  CAS  Google Scholar 

  57. Li S, Christensen C, Køhler LB, Kiselyov VV, Berezin V et al (2009) Agonists of fibroblast growth factor receptor induce neurite outgrowth and survival of cerebellar granule neurons. Dev Neurobiol 69:837–854

    Article  PubMed  CAS  Google Scholar 

  58. Anderson a A, Kendal CE, Garcia-Maya M, Kenny AV, Morris-Triggs a S et al (2005) A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival. J Neurochem 95:570–583

    Article  PubMed  CAS  Google Scholar 

  59. Popov VI, Medvedev NI, Kraev IV, Gabbott PL, Davies HA et al (2008) A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study. Eur J Neurosci 27:301–314

    Article  PubMed  Google Scholar 

  60. Bourne J, Harris KM (2007) Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol 17:381–386

    Article  PubMed  CAS  Google Scholar 

  61. Medvedev NI, Popov VI, Rodriguez Arellano JJ, Dallérac G, Davies HA et al (2010) The N-methyl-D-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat. Neuroscience 165:1170–1181

    Article  PubMed  CAS  Google Scholar 

  62. Medvedev NI, Popov VI, Dallérac G, Davies HA, Laroche S et al (2010) Alterations in synaptic curvature in the dentate gyrus following induction of long-term potentiation, long-term depression, and treatment with the N-methyl-D-aspartate receptor antagonist CPP. Neuroscience 171:390–397

    Article  PubMed  CAS  Google Scholar 

  63. Durbec P, Cremer H (2001) Revisiting the function of PSA-NCAM in the nervous system. Mol Neurobiol 24:53–64

    Article  PubMed  CAS  Google Scholar 

  64. Bonfanti L (2006) PSA-NCAM in mammalian structural plasticity and neurogenesis. Prog Neurobiol 80:129–164

    Article  PubMed  CAS  Google Scholar 

  65. Ming G-L, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70:687–702

    Article  PubMed  CAS  Google Scholar 

  66. Seri B, García-Verdugo JM, Collado-Morente L, McEwen BS, Alvarez-Buylla A (2004) Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J Comp Neurol 478:359–378

    Article  PubMed  Google Scholar 

  67. Seki T, Arai Y (1999) Temporal and spacial relationships between PSA-NCAM-expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus. J Comp Neurol 410:503–513

    Article  PubMed  CAS  Google Scholar 

  68. Zhao C, Teng EM, Summers RG, Ming G-L, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci: Off J Soc Neurosci 26:3–11

    Article  CAS  Google Scholar 

  69. Hastings NB, Gould E (1999) Rapid extension of axons into the CA3 region by adult-generated granule cells. J Comp Neurol 413:146–154

    Article  PubMed  CAS  Google Scholar 

  70. Schuster T, Krug M, Stalder M, Hackel N, Gerardy-Schahn R et al (2001) Immunoelectron microscopic localization of the neural recognition molecules L1, NCAM, and its isoform NCAM180, the NCAM-associated polysialic acid, beta1 integrin and the extracellular matrix molecule tenascin-R in synapses of the adult rat hippocampus. J Neurobiol 49:142–158

    Article  PubMed  CAS  Google Scholar 

  71. Seki T, Arai Y (1993) Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat. J Neurosc: Off J Soc Neurosci 13:2351–2358

    CAS  Google Scholar 

  72. Gascon E, Vutskits L, Jenny B, Durbec P, Kiss JZ (2007) PSA-NCAM in postnatally generated immature neurons of the olfactory bulb: a crucial role in regulating p75 expression and cell survival. Development (Cambridge, England) 134:1181–1190

    Article  CAS  Google Scholar 

  73. Ono K, Tomasiewicz H, Magnuson T, Rutishauser U (1994) N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 13:595–609

    Article  PubMed  CAS  Google Scholar 

  74. Aonurm-Helm A, Jurgenson M, Zharkovsky T, Sonn K, Berezin V et al (2008) Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL. Eur J Neurosci 28:1618–1628

    Article  PubMed  Google Scholar 

  75. Vutskits L, Gascon E, Zgraggen E, Kiss JZ (2006) The polysialylated neural cell adhesion molecule promotes neurogenesis in vitro. Neurochem Res 31:215–225

    Article  PubMed  CAS  Google Scholar 

  76. Amoureux MC, Cunningham BA, Edelman GM, Crossin KL (2000) N-CAM binding inhibits the proliferation of hippocampal progenitor cells and promotes their differentiation to a neuronal phenotype. J Neurosci: Off J Soc Neurosci 20:3631–3640

    CAS  Google Scholar 

  77. Hildebrandt H, Mühlenhoff M, Weinhold B, Gerardy-Schahn R (2007) Dissecting polysialic acid and NCAM functions in brain development. J Neurochem 103:56–64

    Article  PubMed  CAS  Google Scholar 

  78. Markram K, Lopez Fernandez MA, Abrous DN, Sandi C (2007) Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction. Neurobiol Learn Mem 87:573–582

    Article  PubMed  CAS  Google Scholar 

  79. Angata K, Long JM, Bukalo O, Lee W, Dityatev A et al (2004) Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior. J Biol Chem 279:32603–32613

    Article  PubMed  CAS  Google Scholar 

  80. Röckle I, Seidenfaden R, Weinhold B, Mühlenhoff M, Gerardy-Schahn R et al (2008) Polysialic acid controls NCAM-induced differentiation of neuronal precursors into calretinin-positive olfactory bulb interneurons. Dev Neurobiol 68:1170–1184

    Article  PubMed  CAS  Google Scholar 

  81. Ojo B, Gabbott PL, Rezaie P, Corbett N, Medvedev NI, et al. (2012) An NCAM Mimetic, FGL, Alters Hippocampal Cellular Morphometry in Young Adult (4 Month-Old) Rats. Neurochemical research

  82. Roullet P, Mileusnic R, Rose SP, Sara SJ (1997) Neural cell adhesion molecules play a role in rat memory formation in appetitive as well as aversive tasks. Neuro Report 8:1907–1911

    CAS  Google Scholar 

  83. Scholey AB, Rose SP, Zamani MR, Bock E, Schachner M (1993) A role for the neural cell adhesion molecule in a late, consolidating phase of glycoprotein synthesis six hours following passive avoidance training of the young chick. Neuroscience 55:499–509

    Article  PubMed  CAS  Google Scholar 

  84. Mileusnic R, Rose SP, Lancashire C, Bullock S (1995) Characterisation of antibodies specific for chick brain neural cell adhesion molecules which cause amnesia for a passive avoidance task. J Neurochem 64:2598–2606

    Article  PubMed  CAS  Google Scholar 

  85. Arami S, Jucker M, Schachner M, Welzl H (1996) The effect of continuous intraventricular infusion of L1 and NCAM antibodies on spatial learning in rats. Behav Brain Res 81:81–87

    Article  PubMed  CAS  Google Scholar 

  86. Doyle E, Nolan PM, Bell R, Regan CM (1992) Intraventricular infusions of anti-neural cell adhesion molecules in a discrete posttraining period impair consolidation of a passive avoidance response in the rat. J Neurochem 59:1570–1573

    Article  PubMed  CAS  Google Scholar 

  87. Venero C, Herrero AI, Touyarot K, Cambon K, López-Fernández MA et al (2006) Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory. Eur J Neurosci 23:1585–1595

    Article  PubMed  Google Scholar 

  88. Merino JJ, Cordero MI, Sandi C (2000) Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity. Eur J Neurosci 12:3283–3290

    Article  PubMed  CAS  Google Scholar 

  89. Skibo GG, Davies HA, Rusakov DA, Stewart MG, Schachner M (1998) Increased immunogold labelling of neural cell adhesion molecule isoforms in synaptic active zones of the chick striatum 5–6 hours after one-trial passive avoidance training. Neuroscience 82:1–5

    Article  PubMed  CAS  Google Scholar 

  90. O’Connell C, O’Malley A, Regan CM (1997) Transient, learning-induced ultrastructural change in spatially-clustered dentate granule cells of the adult rat hippocampus. Neuroscience 76:55–62

    Article  PubMed  Google Scholar 

  91. Fox GB, O’Connell AW, Murphy KJ, Regan CM (1995) Memory consolidation induces a transient and time-dependent increase in the frequency of neural cell adhesion molecule polysialylated cells in the adult rat hippocampus. J Neurochem 65:2796–2799

    Article  PubMed  CAS  Google Scholar 

  92. Doyle E, Nolan PM, Bell R, Regan CM (1992) Hippocampal NCAM180 transiently increases sialylation during the acquisition and consolidation of a passive avoidance response in the adult rat. J Neurosci Res 31:513–523

    Article  PubMed  CAS  Google Scholar 

  93. Seymour CM, Foley AG, Murphy KJ, Regan CM (2008) Intraventricular infusions of anti-NCAM PSA impair the process of consolidation of both avoidance conditioning and spatial learning paradigms in Wistar rats. Neuroscience 157:813–820

    Article  PubMed  CAS  Google Scholar 

  94. Lopez-Fernandez MA, Montaron M-F, Varea E, Rougon G, Venero C et al (2007) Upregulation of polysialylated neural cell adhesion molecule in the dorsal hippocampus after contextual fear conditioning is involved in long-term memory formation. J Neurosci: Off J Soc Neurosci 27:4552–4561

    Article  CAS  Google Scholar 

  95. Florian C, Foltz J, Norreel J-C, Rougon G, Roullet P (2006) Post-training intrahippocampal injection of synthetic poly-alpha-2,8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice. Learning Memory (Cold Spring Harbor, NY) 13:335–341

    Article  CAS  Google Scholar 

  96. O’Malley A, O’Connell C, Regan CM (1998) Ultrastructural analysis reveals avoidance conditioning to induce a transient increase in hippocampal dentate spine density in the 6 hour post-training period of consolidation. Neuroscience 87:607–613

    Article  PubMed  Google Scholar 

  97. Køhler LB, Christensen C, Rossetti C, Fantin M, Sandi C et al (2010) Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning. Eur J Cell Biol 89:817–827

    Article  PubMed  CAS  Google Scholar 

  98. Foley AG, Hartz BP, Gallagher HC, Rønn LC, Berezin V et al (2000) A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning. J Neurochem 74:2607–2613

    Article  PubMed  CAS  Google Scholar 

  99. Cambon K, Venero C, Berezin V, Bock E, Sandi C (2003) Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning. Neuroscience 122:183–191

    Article  PubMed  CAS  Google Scholar 

  100. Rizhova L, Klementiev B, Cambon K, Venero C, Sandi C (2007) Effect of P2 a peptide derived from a homophilic binding site in the neural cell adhesion molecule on learning and memory in rats. Neuroscience 149:931–942

    Article  PubMed  CAS  Google Scholar 

  101. Secher T, Novitskaia V, Berezin V, Bock E, Glenthøj B et al (2006) A neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention. Neuroscience 141:1289–1299

    Article  PubMed  CAS  Google Scholar 

  102. Cam MC, Brownsey RW, McNeill JH (2000) Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 78:829–847

    Article  PubMed  CAS  Google Scholar 

  103. Cam MC, Rodrigues B, McNeill JH (1999) Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes. Eur J Endocr/Eur Fed Endocr Soc 141:546–554

    Article  CAS  Google Scholar 

  104. Getz GS, Wool GD, Reardon CA (2010) HDL apolipoprotein-related peptides in the treatment of atherosclerosis and other inflammatory disorders. Curr Pharm Des 16:3173–3184

    Article  PubMed  CAS  Google Scholar 

  105. Sharifov OF, Nayyar G, Garber DW, Handattu SP, Mishra VK et al (2011) Apolipoprotein E mimetics and cholesterol-lowering properties. Am J Cardiovasc Drugs:Drugs, Devices Interv 11:371–381

    Article  CAS  Google Scholar 

  106. Gordon SM, Davidson WS (2012) Apolipoprotein A-I mimetics and high-density lipoprotein function. Curr Opin Endocrinol Diabetes Obes 19:109–114

    PubMed  CAS  Google Scholar 

  107. Klementiev B, Novikova T, Novitskaya V, Walmod PS, Dmytriyeva O et al (2007) A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35. Neuroscience 145:209–224

    Article  PubMed  CAS  Google Scholar 

  108. Downer EJ, Cowley TR, Cox F, Maher FO, Berezin V et al (2009) A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation. J Neurochem 109:1516–1525

    Article  PubMed  CAS  Google Scholar 

  109. Secher T, Berezin V, Bock E, Glenthøj B (2009) Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats. Behav Brain Res 199:288–297

    Article  PubMed  CAS  Google Scholar 

  110. Skibo GG, Lushnikova IV, Voronin KY, Dmitrieva O, Novikova T et al (2005) A synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo. Eur J Neurosci 22:1589–1596

    Article  PubMed  Google Scholar 

  111. Anand R, Seiberling M, Kamtchoua T, Pokorny R (2007) Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers. Clin Pharmacokinet 46:351–358

    Article  PubMed  CAS  Google Scholar 

  112. Burgess A, Saini S, Weng Y-Q, Aubert I (2009) Stimulation of choline acetyltransferase by C3d, a neural cell adhesion molecule ligand. J Neurosci Res 87:609–616

    Article  PubMed  CAS  Google Scholar 

  113. Klementiev B, Bichevaja N, Novikova T, Chebotar N, Bock E et al (2002) A peptide agonist of the neural cell adhesion molecule (NCAM), C3, protects against developmental defects induced by a teratogen pyrimethamine. Int J Dev Neurosci : off J Int Soc Dev Neurosci 20:527–536

    Article  CAS  Google Scholar 

  114. Sakai A, Asada M, Seno N, Suzuki H (2008) Involvement of neural cell adhesion molecule signaling in glial cell line-derived neurotrophic factor-induced analgesia in a rat model of neuropathic pain. Pain 137:378–388

    Article  PubMed  CAS  Google Scholar 

  115. Marino MJ, Awad H, Poisik O, Wittmann M, Conn PJ (2002) Localization and physiological roles of metabotropic glutamate receptors in the direct and indirect pathways of the basal ganglia. Amino Acids 23:185–191

    Article  PubMed  CAS  Google Scholar 

  116. Zhang Y, Ghadiri-Sani M, Zhang X, Richardson PM, Yeh J et al (2007) Induced expression of polysialic acid in the spinal cord promotes regeneration of sensory axons. Mol Cell Neurosci 35:109–119

    Article  PubMed  CAS  Google Scholar 

  117. Zhang Y, Zhang X, Wu D, Verhaagen J, Richardson PM et al (2007) Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning lesion promote regeneration of sensory axons into spinal cord. Mol Ther: J Am Soc Gene Ther 15:1796–1804

    Article  CAS  Google Scholar 

  118. Medvedev NI, Dallérac G, Popov VI, Rodriguez Arellano JJ, Davies a H et al (2012) Multiple spine boutons are formed after long-lasting LTP in the awake rat. Brain Struct Funct. doi:10.1007/s00429-012-0488-0

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Pr. Elisabeth Bock who coordinated the EU FP6 Promemoria program (Contract No. 512012) which supported their work on NCAM and plasticity [29, 38, 61, 62, 118].

Author information

Author notes

  1. Glenn Dallérac

    Present address: Centre Interdisciplinaire de Recherche en Biologie, CNRS UMR 7241/INSERM U1050, Collège de France, 11 Place Marcelin Berthelot, Paris, 75005, France

Authors and Affiliations

  1. Centre de Neurosciences Paris-Sud, UMR, 8195, Univ Paris-Sud, Orsay, 91405, France

    Glenn Dallérac & Valérie Doyère

  2. CNRS, Orsay, 91405, France

    Glenn Dallérac & Valérie Doyère

  3. Centre de Recherches sur la Cognition Animale, Université de Toulouse, UPS, 118 route de Narbonne, Toulouse Cedex 4, 31062, France

    Claire Rampon

  4. Centre de Recherches sur la Cognition Animale, CNRS, Toulouse, 31062, France

    Claire Rampon

Authors
  1. Glenn Dallérac
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Rampon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valérie Doyère
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Glenn Dallérac or Valérie Doyère.

Additional information

Special Issue: In Honor of Elisabeth Bock.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dallérac, G., Rampon, C. & Doyère, V. NCAM Function in the Adult Brain: Lessons from Mimetic Peptides and Therapeutic Potential. Neurochem Res 38, 1163–1173 (2013). https://doi.org/10.1007/s11064-013-1007-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-013-1007-2

Keywords

Search

Navigation