Dendritic Spine and Synapse Morphological Alterations Induced by a Neural Cell Adhesion Molecule Mimetic

  • Michael StewartEmail author
  • Victor Popov
  • Nikolai Medvedev
  • Paul Gabbott
  • Nicola Corbett
  • Igor Kraev
  • Heather Davies
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 663)


The neural cell adhesion molecule (NCAM) is a glycoprotein expressed on the surface of neurons and glial cells. It plays a key role in morphogenesis of the nervous system, regeneration of damaged neural tissue and synaptic plasticity. The extracellular domain of NCAM engages in homophilic interactions (NCAM binding to NCAM) and in heterophilic interactions between NCAM and other proteins such as the fibroblast growth factor (FGF) receptor. It promotes synaptogenesis and activity-dependent remodelling of synapses but less is known of its influence on synaptic and dendritic morphology. Recently, quantitative electron microscopy and 3-dimensional reconstruction (3-D) of ultrathin serial sections has been used to examine the morphology of synapses and dendritic spines in the hippocampus of rats treated with a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, FGL-peptide (an NCAM mimetic). These data show clearly that the FGL peptide has marked influences on both spine and synaptic form.


Dendritic spine PSD 3-D reconstruction Ultrastructure NCAM-mimetic 



Supported by EU FPVI Promemoria Contract No. 512012 and to V.I.P. (RFBR grant 05-04-49635-а) and I.V.K. (grant MK-424.2007.4).


  1. 1.
    Persohn E, Schachner M (1987) Immunoelectron microscopic localization of the neural cell adhesion molecules L1 and N-CAM during postnatal development of the mouse cerebellum. J Cell Biol 105:569-576PubMedCrossRefGoogle Scholar
  2. 2.
    Schuster T, Krug M, Stalder M 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 49:142-158PubMedCrossRefGoogle Scholar
  3. 3.
    Cambon K, Hansen SM, Venero C et al (2004) A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci 24:4197-4204PubMedCrossRefGoogle Scholar
  4. 4.
    Venero C, Herrero AI, Touyarot K et al (2006) Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory. Eur J NeuroSci 23:1585-1595PubMedCrossRefGoogle Scholar
  5. 5.
    Dityatev A, Dityateva G, Sytnyk V et al (2004) Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci 24:9372-9382PubMedCrossRefGoogle Scholar
  6. 6.
    Skibo G, Davies H, Rusakov D et al (1998) Increased immunogold labelling of N-CAM isoforms in striatum 6h after avoidance training. Neuroscience 82:1-5PubMedCrossRefGoogle Scholar
  7. 7.
    Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31-39PubMedCrossRefGoogle Scholar
  8. 8.
    Schuster T, Krug M, Hassan H et al (1998) Increase in proportion of hippocampal spine synapses expressing neural cell adhesion molecule NCAM180 following long-term potentiation. J Neurobiol 37:359-372PubMedCrossRefGoogle Scholar
  9. 9.
    Stoenica L, Senkov O, Gerardy-Schahn R 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 23:2255-2264PubMedCrossRefGoogle Scholar
  10. 10.
    Christensen C, Lauridsen JB, Berezin V et al (2006) The neural cell adhesion molecule binds to fibroblast growth factor receptor 2. FEBS Lett 580:3386-3390PubMedCrossRefGoogle Scholar
  11. 11.
    Kiselyov VV, Skladchikova G, Hinsby AM et al (2003) Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure 11:691-701PubMedCrossRefGoogle Scholar
  12. 12.
    Neiiendam JL, Køhler LB, Christensen C et al (2004) An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons. J Neurochem 91:920-935PubMedCrossRefGoogle Scholar
  13. 13.
    Secher T, Novitskaia V, Berezin V et al (2007) 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 141:1289-1299CrossRefGoogle Scholar
  14. 14.
    Klementiev B, Novikova T, Novitskaya V et al (2007) A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Aβ 25-35. Neuroscience 145:209-224PubMedCrossRefGoogle Scholar
  15. 15.
    Dhanrajan TM, Lynch MA, Kelly A et al (2004) Expression of long-term potentiation in aged rats involves perforated synapses but dendritic spine branching results from high-frequency stimulation alone. Hippocampus 14:255-264PubMedCrossRefGoogle Scholar
  16. 16.
    Loane DJ, Deighan BF, Clarke RM et al (2009) Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain. Neurobiol Aging 30:920-931PubMedCrossRefGoogle Scholar
  17. 17.
    Maher FO, Nolan Y, Lynch MA (2005) Downregulation of IL-4-induced signalling in hippocampus contributes to deficits in LTP in the aged rat. Neurobiol Aging 26:717-728PubMedCrossRefGoogle Scholar
  18. 18.
    PopovVI Medvedev NI, Kraev I 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 27:301-314CrossRefGoogle Scholar
  19. 19.
    Marrone DF, Petit TL (2002) The role of synaptic morphology in neural plasticity: structural interactions underlying synaptic power. Brain Res Rev 38:291-308PubMedCrossRefGoogle Scholar
  20. 20.
    Marrone DF, LeBoutillier JC, Petit TL (2004) Changes in synaptic ultrastructure during reactive synaptogenesis in the rat dentate gyrus. Brain Res 1005:124-136PubMedCrossRefGoogle Scholar
  21. 21.
    Popov VI, Davies HA, Rogachevsky VV et al (2004) Remodelling of synaptic morphology but unchanged synaptic density during late phase long-term potentiation (LTP): a serial section electron micrograph study in the dentate gyrus in the anaesthetised rat. Neuroscience 128:251-262PubMedCrossRefGoogle Scholar
  22. 22.
    Cooney JR, Hurlburt JL, Selig DK et al (2002) Endosomal compartments serve multiple hippocampal dendritic spines from a widespread rather than a local store of recycling membrane. J Neurosci 22:2215-2224PubMedGoogle Scholar
  23. 23.
    Murk JL, Humbel BM, Ziese U et al (2003) Endosomal compartmentalization in three dimensions: implications for membrane fusion. Proc Natl Acad Sci USA 100:13332-13337PubMedCrossRefGoogle Scholar
  24. 24.
    Kennedy MJ, Ehlers MD (2006) Organelles and trafficking machinery for postsynaptic plasticity. Annu Rev Neurosci 29:325-362PubMedCrossRefGoogle Scholar
  25. 25.
    Ehlers MD (2000) Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting. Neuron 28:511-525PubMedCrossRefGoogle Scholar
  26. 26.
    Corbett NJ, Gabbott PL, Stewart MG et al (2007) A neural cell adhesion molecule mimetic, Fibroblast Growth Loop (FGL), alleviates spine loss induced by β-amyloid25-35 in the rat hippocampus. In: Society for Neuroscience Abstrats (USA) 886.9Google Scholar
  27. 27.
    Geinisman Y (2000) Structural synaptic modifications associated with hippocampal LTP and behavioral learning. Cereb Cortex 10:952-962PubMedCrossRefGoogle Scholar
  28. 28.
    Bourne J, Harris KM (2007) Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol 17:381-386PubMedCrossRefGoogle Scholar
  29. 29.
    Stewart MG, Medvedev NI, Popov VI et al (2005) Chemically induced long-term potentiation increases the number of perforated and complex postsynaptic densities but does not alter dendritic spine volume in CA1 of adult mouse hippocampal slices. Eur J NeuroSci 21:3368-3378PubMedCrossRefGoogle Scholar
  30. 30.
    Ganeshina O, Berry RW, Petralia RS et al (2004) Differences in the expression of AMPA and NMDA receptors between axospinous perforated and nonperforated synapses are related to the configuration and size of postsynaptic densities. J Comp Neurol 468:86-95PubMedCrossRefGoogle Scholar
  31. 31.
    Ganeshina O, Berry RW, Petralia RS et al (2004) Synapses with a segmented, completely partitioned postsynaptic density express more AMPA receptors than other axospinous junctions. Neuroscience 125:615-623PubMedCrossRefGoogle Scholar
  32. 32.
    Nicholson DA, Trana R, Katz Y et al (2006) Distance-dependent differences in synapse number and AMPA receptor expression in hippocampal CA1 pyramidal neurons. Neuron 50:431-442PubMedCrossRefGoogle Scholar
  33. 33.
    Sorkin A (2004) Cargo recognition during clathrin-mediated endocytosis: a team effort. Curr Opin Cell Biol 16:392-399PubMedCrossRefGoogle Scholar
  34. 34.
    Stewart MG, Davies HA, Sandi C et al (2005) Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: a three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities. Neuroscience 131:43-54PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michael Stewart
    • 1
    Email author
  • Victor Popov
  • Nikolai Medvedev
  • Paul Gabbott
  • Nicola Corbett
  • Igor Kraev
  • Heather Davies
  1. 1.Department of Life Sciences, Faculty of SciencesThe Open UniversityMilton KeynesUK

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