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Cellular and Molecular Neurobiology

, Volume 5, Issue 1–2, pp 183–207 | Cite as

The role of brain extracellular proteins in neuroplasticity and learning

  • Victor E. Shashoua
Article

Summary

  1. 1.

    Double labeling studies of the pattern of protein synthesis in goldfish and mouse brain identified a class of glycoproteins (the ependymins) whose turnover rate was enhanced after training. A variety of control experiments indicated that these macromolecules have an important role in the molecular and cell biology of learning. Antisera to the ependymins when injected into the brains of trained goldfish cause amnesia of a newly acquired behavior.

     
  2. 2.

    Isolation and localization studies by immunocytochemical methods indicate that the ependymins are released into the brain extracellular fluid by a class of neurosecretory cells. In mammalian brain ependymin-containing cells are highly concentrated in the limibic system.

     
  3. 3.

    The ependymins are constituted from two disulfide-linked acidic polypeptide chains (M.W. 37K and 31K). They contain at least 5% covalently bound carbohydrate per chain with mannose, galactose, N-acetylglucosamine and N-acetylneuraminic acid as the predominant components.

     
  4. 4.

    The highly soluble ependymins can rapidly polymerize to form an insoluble fibrous matrix if calcium is removed from solution by the addition of a Ca2+ -chelating agent or dialysis.

     
  5. 5.

    The self-aggregation property of the ependymins can be triggered by the depletion of Ca2+ from the extracellular space. Studies of the kinetics of the aggregation phenomenon by measurements of turbidity changes indicate that the process can be terminated but not reversed by restoring Ca2+ to its normal CSF level.

     
  6. 6.

    Immunohistochemical studies of the brains of trained goldfish show the presence of punctate statining sites in the perimeter of certain cells located in specific brain regions. This suggests that ependymin aggregation might occurin vivo during learning.

     
  7. 7.

    A molecular hypothesis relating the aggregation properties of the ependymins to neuroplasticity and learning is proposed.

     

Key words

glycoproteins ependymins learning protein aggregation goldfish extracellular matrix mice 

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References

  1. Alkon, D. L. (1980). Cellular analysis of a gastropod (Hermissenda crassicornis) model of associative learning.Biol. Bull. 159505–560.Google Scholar
  2. Appel, S. H. (1967). Turnover of brain messenger RNA.Nature (Lond.)2131253–1254.Google Scholar
  3. Benowitz, L. I., and Shashoua, V. E. (1977). Localization of a brain protein metabolically linked with behavioral plasticity in the goldfish.Brain Res. 136227–242.Google Scholar
  4. Bonner-Frazer, M., and Cohen, A. M. (1980). Analysis of the neural crest ventral pathway using injected tracer cells.Dev. Biol. 77130–141.Google Scholar
  5. Bourre, J. M., Pollet, S., Paturneau-Jovas, M., and Baumann, N. (1977). Function and biosynthesis of lipids.Adv. Exp. Med. Biol. 83103–109.Google Scholar
  6. Chaffee, J., and Schachner, M. (1978). A new cell-surface antigen of brain kidney and spermatozoa.Dev. Biol. 62173–184.Google Scholar
  7. Carew, T. L., Walters, E. T., and Kandel, E. R. (1981). Associative learning inAplysia: Cellular correlates supporting a conditioned fear hypothesis.Science 211501–504.Google Scholar
  8. Cserr, H. F., and Ostrach, L. H. (1974). On the presence of subarachnoid fluid in the mudpuppy,Necturus maculosus.Comp. Biochem. Physiol. 48A145–151.Google Scholar
  9. Greene, E., Stauff, C., and Walters, J. (1972). Recovery of function with two-stage lesion of the fornix.Exp. Neurol. 3714–22.Google Scholar
  10. Hesse, G., Hofstein, R., and Shashoua, V. E. (1984). Protein release from hippocampus in vitro.Brain Res. 30561–66.Google Scholar
  11. Hofstein, R., Hesse, G., and Shashoua, V. E. (1983). Protein of the extracellular fluid of mouse brain: Extraction and partial characterization.J. Neurochem. 401448–1455.Google Scholar
  12. Krnjević, K. (1985). InNeural Mechanisms of Conditioning (Alkon, D. L., and Woody, C., Eds.), Plenum Press, New York (in preparation).Google Scholar
  13. Krnjević, K., Morris, M. E., and Reiffenstein, R. J. (1982a). Stimulation-evoked protein changes in extracellular K+ and Ca2+ in pyramidel layers of the rat's hippocampus.Can. J. Physiol. Pharmacol. 601643–1657.Google Scholar
  14. Krnjević, K., Morris, M. E., Reiffenstein, R. J., and Ropert, N. (1982b). Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus.Can. J. Physiol. Pharmacol. 601658–1671.Google Scholar
  15. Lajtha, A., and Toth, J. (1966). Instability of cerebral proteins.J. Biochem. Biophys. Res. Comm. 23249–299.Google Scholar
  16. Lynch, G. S., and Schubert, P. (1980). The use of in vitro brain slices for multidisciplinary studies of synaptic function.Annu. Rev. Neurosci. 31–22.Google Scholar
  17. Majocha, R. E., Schmidt, R., and Shashoua, V. E. (1982). Cultures of zona ependyma cells of goldfish brain: An immunological study of the synthesis and release of ependymins.J. Neurosci. Res. 8331–342.Google Scholar
  18. McCormick, D. A., Clark, G. A., Lavond, D. G., and Thompson, R. F. (1982). Initial localization of the memory trace for a basic form of learning.Proc. Natl. Acad. Sci. USA 792731–2735.Google Scholar
  19. McMahan, V. J., Edgington, D. R., and Kuffler, D. P. (1980). Factors that influence regeneration of the neuromuscular junction.J. Exp. Biol. 8931–38.Google Scholar
  20. Reinhold, V. N. (1972). Gas-liquid chromatographic analysis of constituent carbohydrates in glycoproteins. InMethods of Enzymology, Vol. 25 (Hirs, C. H., and Timasheff, S. N., Eds.), Academic Press, New York, pp. 244–249.Google Scholar
  21. Sanes, J. R. (1983). Roles of extracellular matrix in neural development.Annu. Rev. Physiol. 45581–600.Google Scholar
  22. Schmidt, R., and Shashoua, V. E. (1981). A radioimmunoassay for ependyminsβ andγ: Two goldfish brain proteins involved in behavioral plasticity.J. Neurochem. 361368–1377.Google Scholar
  23. Schmidt, R., and Shashoua, V. E. (1983). Structural and metabolic relationships between goldfish brain glycoproteins participating in functional plasticity of the central nervous system.J. Neurochem. 40652–660.Google Scholar
  24. Shashoua, V. E. (1968). RNA changes in goldfish brain during learning.Nature (Lond.)217238–240.Google Scholar
  25. Shashoua, V. E. (1972). A multistage transduction model for information processing in the nervous system.Int. J. Neurosci. 3299–304.Google Scholar
  26. Shashoua, V. E. (1976). Brain metabolism and the acquisition of hew behaviors. I. Evidence for specific changes in the pattern of protein synthesis.Brain Res. 111347–367.Google Scholar
  27. Shashoua, V. E. (1977a). Brain metabolism and the acquisition of new behaviors. II. Immunological studies of theα, β andγ proteins of goldfish brain.Brain Res. 122113–124.Google Scholar
  28. Shashoua, V. E. (1977b). Brain protein metabolism and the acquisition of new patterns of behavior.Proc. Natl. Acad. Sci. USA 741743–1747.Google Scholar
  29. Shashoua, V. E. (1979). Brain metabolism and the acquisition of new behaviors. III. Evidence for secretion of two proteins into the brain extracellular fluid after training.Brain Res. 166349–358.Google Scholar
  30. Shashoua, V. E. (1981). Extracellular fluid proteins of goldfish brain: Studies of concentration and labeling patterns.Neurochem. Res. 6(10):1129–1147.Google Scholar
  31. Shashoua, V. E. (1982). Molecular and cell biological aspects of learning: Towards a theory of memory.Adv. Cell. Neurobiol. 397–141.Google Scholar
  32. Shashoua, V. E. (1984). The role of extracellular glycoproteins in CNS plasticity: Calcium effects on polymerization.Soc. Neurosci. 10195.12.Google Scholar
  33. Shashoua, V. E., and Moore, M. E. (1978). Effect of antisera toβ andγ goldfish brain proteins on the retention of a newly acquired behavior.Brain Res. 148441–449.Google Scholar
  34. Shashoua, V. E., and Moore, M. E. (1980). Enhanced labeling of ECF proteins in mouse brain after training.Neurosci. Abstr. 6290.4.Google Scholar
  35. Shashoua, V. E., and Moore, M. E. (1985). Effect of training on mammalian brain protein synthesis. I. Evidence for specific changes (submitted for publication).Google Scholar
  36. Sternberger, L. A. (1979).Immunocytochemistry, J. Wiley & Sons, New York.Google Scholar
  37. Thompson, R. E., Berger, T. W., and Madden, J. IV (1983). Cellular processes of learning and memory in the mammalian CNS.Ann. Rev. Neurosci. 6447–492.Google Scholar

Copyright information

© Plenum Publishing Corporation 1985

Authors and Affiliations

  • Victor E. Shashoua
    • 1
  1. 1.Ralph Lowell LaboratoriesMailman Research Center, McLean Hospital, Harvard Medical SchoolBelmontUSA

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