Skip to main content
Log in

Polysialytation as a regulator of neural plasticity in rodent learning and aging

  • Original Ariticles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Although generally accepted to play an important role in development, the precise functional significance of NCAM remains to be elucidated. Correlative and interventive studies suggest a role for polysialylated NCAM in neurite elaboration. In the adult NCAM polysialylation continues to be expressed in regions of the central nervous system which retain neuroplastic potential. During memory formation modulation of polysialylation on the synapse-enriched isoform of NCAM occurs in the hippocampus. The polysialylated neurons of this structure have been located at the border of the granule cell layer and hilar region of the dentate and their number increases dramatically during memory consolidation. The converse is also true for a profound decline in the basal number of polysialylated neurons occurs with ageing when neural plasticity becomes attenuated. In conclusion, it is suggested that NCAM polysialylation regulates ultrastructural plasticity associated with synaptic elaboration.

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

Access this article

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

Abbreviations

PSA:

polysialic acid

NCAM:

neural cell adhesion molecule

SGL:

sub-granular cell layer

MF:

mossy fibers

References

  1. Meier, E., Regan, C., Balázs, R., and Wilkin, G. P. 1982. Specific recognition of the neuronal cell surface by an antiserum raised against plasma membrane preparations of immature rat cerebellum. Neurochem. Res. 7:1031–1043.

    PubMed  Google Scholar 

  2. Meier, E., Regan, C. M., and Balázs, R. 1984. Changes in the expression of a neuronal surface protein during development of cerebellar neurones in vivo and in culture. J. Neurochem. 43: 1328–1335.

    PubMed  Google Scholar 

  3. Annunziata, P., Regan, C., and Balázs, R. 1983. Development of cerebellar cells in neuron-enriched cultures. Cell surface proteins. Devel. Brain. Res. 8:261–273.

    Google Scholar 

  4. Jorgensen, O. S. 1976. Localization of the antigens D1, D2 and D3 in the rat brain synaptic membrane. J. Neurochem. 27:1223–1227.

    PubMed  Google Scholar 

  5. Noble, M., Albrechsten, M., Moller, C., Lyles, J., Bock, E., Goridis, C., Watanabe, M., and Rutishauser U. 1985. Glial cells express N-CAM/D2-CAM like polypeptides in vitro. Nature 316: 725–728.

    PubMed  Google Scholar 

  6. Jorgensen, O. S., Delouvee, A., Thiery, J.-P., and Edelman, G. M. 1980. The nervous system specific protein D2 is involved in adhesion among neurites from cultured rat ganglia. FEBS Lett. 111: 39–42.

    PubMed  Google Scholar 

  7. Walsh, F. S., and Doherty, P. 1991. Structure and function of the gene for neural cell adhesion molecule. Semin. Neurosci. 3:271–284.

    Google Scholar 

  8. Persohn, E., Pollerberg, G. E., and Schachner, M. 1989. Immunoelectron-microscopic localization of the 180kD component of the neural cell adhesion molecule NCAM in postsynaptic membranes. J. Comp. Neurol. 288:92–100.

    PubMed  Google Scholar 

  9. Sheehan, M. C., Halpin, C. I., Regan, C. M., Moran, N. M., and Kilty, C. G. 1986. Purification and characterization of the D2 cell adhesion protein. Analysis of the postnatally regulated polymorphic forms and their cellular distribution. Neurochem. Res. 11: 1333–1346.

    PubMed  Google Scholar 

  10. Pollerberg, E. G., Schachner, M., and Davoust, J. 1986. Differentiation state-dependent surface mobilities of two forms of the neural cell adhesion molecule. Nature 324:462–465.

    PubMed  Google Scholar 

  11. Finne, J., Finne, U., Deagostini-Bazin, H., and Goridis, C. 1983. Occurence of α2–8 linked polysialosyl units in a neural cell adhesion molecule. Biochem. Biophys. Res. Commun. 112:482–487.

    PubMed  Google Scholar 

  12. Livingstone, B. D., Jacobs, J. L., Glick, M. C., and Troy, F. A. 1988. Extended polysialic acid chains (n>55) in glycoproteins from human neuroblastoma cells. J. Biol. Chem. 2163:9443–9448.

    Google Scholar 

  13. Zuber, C., Lackie, P., Catterall, W., and Roth, J. 1992. Polysialic acid is associated with sodium channels and the neural cell adhesion molecule NCAM in adult rat brain. J. Biol. Chem. 267: 9965–9971.

    PubMed  Google Scholar 

  14. Small, S. J., and Akeson, R. A. 1990. Expression of the unique NCAM VASE exon is independently regulated in distinct tissues during development. J. Cell Biol, 111:2089–2096.

    PubMed  Google Scholar 

  15. Thiery, J.-P., Duband, J. P., Rutishauser, U., and Edelman, G. M. 1982. Cell adhesion molecules in early chicken embryogenesis. Proc. Natn. Acad. Sci. U.S.A. 79:6737–6741.

    Google Scholar 

  16. Choung, C.-M., Crossin, K. L. and Edelman, G. M. 1987. Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers. J. Cell Biol. 104:331–342.

    PubMed  Google Scholar 

  17. Doherty, P., Cohen, J., and Walsh, F. S. 1990. Neurite outgrowth in response to transfected N-CAM changes during development and is modulated by polysialic acid. Neuron 5:209–219.

    PubMed  Google Scholar 

  18. Doherty, P., Fruns, M., Seaton, P., Dickson, G., Barton, C. H., Sears, T. A., and Walsh, F. S. 1990. A threshold effect of the major isoforms of NCAM on neurite outgrowth. Nature 343:464–466.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  20. Edelman, G. M. 1984. Cell adhesion and morphogenesis: The regulator hypothesis. Proc. Natl. Acad. Sci. USA 81:1460–1464.

    PubMed  Google Scholar 

  21. Doherty, P., Ashton, S. V., Moore, S. E., and Walsh, F. S. 1991. Morphoregulatory activities of NCAM and N-Cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels. Cell 50:1119–1130.

    Google Scholar 

  22. Tomasiewicz, H., Ono, K., Yee, D., Thompson, C., Goridis, C., Rutishauser, U., and Magnuson, T. 1993. Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system. Neuron 11:1163–1174.

    PubMed  Google Scholar 

  23. Cremer, H., Lange, R., Christoph, A., Plomann, M., Vopper, G., Roes, J., Brown, R., Baldwin, S., Kraemer, P., Scheff, S., Barthels, D., Rajewsky, K., and Willie, W. (1994) Inactivation of the NCAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367:455–459.

    PubMed  Google Scholar 

  24. Squire, L. R. (1987). Memory and Brain. Oxford Press, New York.

    Google Scholar 

  25. Miragall, F., Kadmon, G., Husmann, M., and Schachner, M. 1988. Expression of cell adhesion molecules in the olfactory system of the adult mouse: presence of the embryonic form of NCAM. Devl. Biol. 129:516–531.

    Google Scholar 

  26. Seki, T. and Arai, Y. 1991. Expression of highly polysialylated NCAM in the neocortex and piriform cortex of the developing and the adult rat. Anat. Embryol. 184:395–401.

    PubMed  Google Scholar 

  27. Rougon, G., Dubois, C., Buckley, N., Magnani J. L. and Zollinger, W. 1986. A monoclonal antibody against meningococcus group B polysaccharides distinguishes embryonic from adult N-CAM. J. Cell Biol. 103:2429–2437.

    PubMed  Google Scholar 

  28. Plioplys, A. V., Hemmens, S. E., and Regan, C. M. 1990. Expression of a NCAM serum fragment is depressed in autism. J. Neuropsychiat Clin. Neurosci. 2:413–417.

    Google Scholar 

  29. Doyle, E., Nolan, P., Bell, R., and Regan, C. M. 1992. Hippocampal NCAM 180 transiently increases sialylation during the acquisition and consolidation of a passive response in the adult rat. J. Neurosci. Res. 31:513–523.

    PubMed  Google Scholar 

  30. Paxinos G., and Watson C. 1986. The Rat Brain in Stereotaxic Co-ordinates. 2nd Ed., Academic Press, New York.

    Google Scholar 

  31. Bonfanti, L., Olive, S., Poulain, D., and Theodosis, D. 1992. Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat; an immunohistochemical study. Neurosci 49:419–436.

    Google Scholar 

  32. Seki, T., and Arai, Y. 1993. Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system. Neurosci. Res. 17:265–290.

    PubMed  Google Scholar 

  33. Theodosis, D., Rougon, G., and Poulain, D. 1991. Retention of embryonic features by an adult neuronal system capable of plasticity: embryonic NCAM in the hypothalamo-neurohypophysial system. Proc. Natl. Acad. Sci. USA 88:5494–5498.

    PubMed  Google Scholar 

  34. Doyle, E., and Regan, C. M. 1993. Cholinergic and dopaminergic agents which inhibit a passive avoidance response attenuate the paradigm-specific increases in NCAM sialylation state. J. Neural Transm. 92:33–49.

    Google Scholar 

  35. Doyle, E., Regan, C. M., and Shiotani, T. 1993. Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule-mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat. J. Neurochem. 61:266–272.

    PubMed  Google Scholar 

  36. Doyle, E., Nolan, P., Bell, R., and Regan, C. M. 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.

    PubMed  Google Scholar 

  37. Bailey, C. H., and Kandel, E. R. 1993. Structural changes accompanying memory storage. Annu. Rev. Physiol. 55:397–426.

    PubMed  Google Scholar 

  38. Scholey, A. B., Rose, S. P. R., Zamani, M. R., Bock, E., and 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. Neurosci. 55:499–509.

    Google Scholar 

  39. Seki, T., and 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. Neurosci. 13: 2351–2358.

    PubMed  Google Scholar 

  40. Le Gal La Salle, G., Rougon, G., and Valin, A. 1992. Embryonic form of NCAM in rat hippocampus: its re-expression on glial cells following kainic acid-induced status epilepticus. J. Neurosc. 12: 872–882.

    Google Scholar 

  41. Jucker, M., Oettinger, R., and Battig, K. 1986. Age-related changes in working and reference memory performance and locomotor activity in the Wistar rat. Behav. Neural biol. 50:24–36.

    Google Scholar 

  42. Boss, B. D., Peterson, G. M., and Cowan, W. M. 1985. On the number of neurons in the dentate gyrus of the rat. Brain Res. 338: 144–150.

    PubMed  Google Scholar 

  43. Linnemann, D., Gaardsvoll, H., Olsen, M., and Bock, E. 1993. Expression of NCAM mRNA and polypeptides in ageing rat brain. Int. J. Devl. Neurosci. 11:71–81.

    Google Scholar 

  44. Regan, C. M. 1991. Regulation of neural cell adhesion molecule (NCAM) sialylation state. Int. J. Biochem. 23:513–523.

    PubMed  Google Scholar 

  45. Rougon, G. 1993. Structure, metabolism and cell biology of polysialic acids. Eur. J. Cell Biol. 61:197–207.

    PubMed  Google Scholar 

  46. Breen, K. C., Kelly, P. G., and Regan, C. M. 1987. Postnatal D2-CAM/N-CAM sialylation state is controlled by a developmentally regulated Golgi sialyltransferase. J. Neurochem. 48:1486–1493.

    PubMed  Google Scholar 

  47. Breen, K. C., and Regan, C. M. 1988. Developmental control of N-CAM sialylation state by golgi sialyltransferase isoforms. Development 104:147–154.

    PubMed  Google Scholar 

  48. Moran, N. M., Breen, K. C., and Regan, C. M. 1986. Characterization and cellular localization of a developmentally regulated rat neural sialidase. J. Neurochem. 47:18–22.

    PubMed  Google Scholar 

  49. Breen, K. C., and Regan, C. M. 1986. Synaptosomal sialyltransferase glycosylates surface proteins that are inaccessible to the action of membrane-bound sialidase. J. Neurochem. 47:1176–1180.

    PubMed  Google Scholar 

  50. Alcaraz, G., and Goridis, C. 1991. Biosynthesis and processing of polysialylated NCAM by AtT-20 cells. Eur. J. Cell Biol. 55:165–173.

    PubMed  Google Scholar 

  51. Friedlander, D. R., Brackenbury, R., and Edelman, g. M. 1985. Conversion of embryonic forms of NCAM in vitro results from de novo synthesis of adult forms. J. Cell Biol. 101:412–419.

    PubMed  Google Scholar 

  52. McCoy, R. D., Vimr, E. R., and Troy, F. A. 1985. CMP-NeuNAc: poly-α-2,8-sialosyl sialyltransferase and the biosynthesis of polysialosyl units in neural cell adhesion molecules. J. biol. Chem. 260:12,695–12,699.

    Google Scholar 

  53. Edelman, G. M., and Chuong, C.-M. 1982. Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Proc. Natl. Acad. Sci. U.S.A. 79:7036–7040.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Special issue dedicated to Dr. Robert Balazs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Regan, C.M., Fox, G.B. Polysialytation as a regulator of neural plasticity in rodent learning and aging. Neurochem Res 20, 593–598 (1995). https://doi.org/10.1007/BF01694541

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01694541

Key words

Navigation