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Blocking action of intracellularly injected neuraminidase on central synapses in vivo

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Abstract

The effect of neuraminidase on synaptic transmission was studied at cholinergic and noncholinergic contacts in the buccal and cerebral ganglion of Aplysia. The amplitudes of monosynaptic unitary postsynaptic potentials generated by intracellular stimulation of identified presynaptic neurones were measured as indication for the efficacy of synaptic transmission. Neuraminidase was either intrasomatically injected into a presynaptic neurone, or the whole ganglion was incubated with the enzyme.

Intrasomatic injection of the enzyme resulted in complete failure of synaptic transmission. This effect occurred independently of the transmitter used. The synaptic failure was presynaptic in origin. The biophysical characteristics of an injected neurone, particularly the amplitude and propagation of its action potential, did not appear to be affected by neuraminidase. Synaptic transmission and biophysical membrane properties were unaffected by extracellular neuraminidase.

We conclude that the synaptic blockade is due to the enzyme's action inside the presynaptic nerve ending. It seems most likely that neuraminidase cleaves sialicacid-containing-compounds associated with the nerve terminal surface membrane, probably thus causing failure of transmitter release.

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References

  1. Augustinsson, K.-B., Ekedahl, G.: The properties of neuraminidasetreated serum cholinesterase. Biochim. Biophys. Acta56, 392–393 (1962)

  2. Baux, G., Simonneau, M., Tauc, L.: Transmitter release: ruthenium red used to demonstrate a possible role of sialic acid containing substrates. J. Physiol. (Lond.)291, 161–178 (1979)

  3. Breckenridge, W. C., Gombos, G., Morgan, I. G.: The lipid composition of adult rat brain synaptosomal plasma membranes. Biochim. Biophys. Acta266, 696–707 (1972)

  4. Brodbeck, U., Gentinetta, R., Lundin, S. J.: Multiple forms of a cholinesterase from body muscle and possible role of sialic acid in cholinesterase reaction specificity. Acta Chem. Scand.27, 561–572 (1973)

  5. Brunngraber, E. G., Dekirmenjian, H., Brown, B. D.: The distribution of protein-bound N-acetylneuraminic acid in subcellular fractions of rat brain. Biochem. J.103, 73–78 (1967)

  6. Coggeshall, R. E., Kandel, E. R., Kupfermann, I., Waziri, R.: A morphological and functional study on a cluster of identifiable neurosecretory cells in the abdominal ganglion ofAplysia californica. J. Cell. Biol.31, 363–368 (1966)

  7. Dekirmenjian, H., Brunngraber, E. G.: Distribution of proteinbound N-acetylneuraminic acid in subcellular particulate fractions prepared from rat whole brain. Biochim. Biophys. Acta177, 1–10 (1969)

  8. Drzeniek, R.: Viral and bacterial neuraminidase. Curr. Top. Microbiol. Immunol.59, 35–74 (1972)

  9. Eichberg, J., Whittaker, V. P., Dawson, R. M. C.: The distribution of lipids in subcellular particles of guinea-pig brain. Biochem. J.92, 91–100 (1964)

  10. Gardner, D.: Bilateral symmetry and interneuronal organization in the buccal ganglion ofAplysia. Science173, 550–553 (1971)

  11. Heijlman, J., Roukema, P. A.: Action of calf brain sialidase on gangliosides, sialoglycoproteins and sialoglycopeptides. J. Neurochem.19, 2567–2575 (1972)

  12. Heilbronn, E.: Treatment of horse serum cholinesterase with sialidase. Acta Chem. Scand.16, 516 (1962)

  13. Heilbronn, E., Cedergren, E.: Chemically induced changes in the acetylcholine uptake and storage capacity of brain tissue. In: Conference on the effect of cholinergic mechanisms in the CNS (E. Heilbronn, A. Winter, eds.),pp. 245–269. Stockholm (Sweden): Skoklostu 1970

  14. Hinzen, D. H., Davies, M. A.: Synaptic connexions and related postsynaptic pharmacology studied in the cerebral ganglion ofAplysia. Brain Res.144, 49–62 (1978)

  15. Hughes, G. M., Tauc, L.: The path of giant cell axons inAplysia depilans. Nature191, 404–405 (1961)

  16. Lapetina, E. G., Soto, E. F., De Robertis, E.: Gangliosides and acetylcholinesterase in isolated membranes of rat brain cortex. Biochim. Biophys. Acta135, 33–43 (1967)

  17. Lapetina, E. G., Soto, E. F., De Robertis, E.: Lipids and Proteolipids in isolated subcellular membranes of rat brain cortex. J. Neurochem.15, 437–445 (1968)

  18. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem.193, 265–275 (1951)

  19. Lüben, G., Sedlacek, H. H., Seiler, F. R.: Quantitative experiments on the cell membranes binding of neuraminidase. Behring Inst. Mitt.59, 30–37 (1976)

  20. Öhman, R.: Subcellular fraction of ganglioside sialidase from human brain. J. Neurochem.18, 89–95 (1971)

  21. Rahmann, H., Rösner, H., Breer, H.: A functional model of sialoglyco-macromolecules in synaptic transmission and memory function. J. Theor. Biol.57, 231–237 (1976)

  22. Schengrund, C.-L., Rosenberg, A.: Intracellular location and properties of bovine brain sialidase. J. Biol. Chem.245, 6196–6200 (1970)

  23. Schick, H. J., Zilg, H.: Production and quality control of therapeutically applicableVibrio cholerae neuraminidase (VCN). Dev. Biol. Stand.38, 81–85 (1978)

  24. Seminario, L. M., Hren, N., Gomez, C. J.: Lipid distribution in subcellular fractions of the rat brain. J. Neurochem.11, 197–207 (1964)

  25. Svensmark, O., Kristensen, P.: Electrophoretic mobility of sialidasetreated human serum cholinesterase. Dan. Med. Bull.9, 16–17 (1962)

  26. Tauc, L., Hinzen, D. H.: Neuraminidase: its effect on synaptic transmission. Brain Res.80, 340–344 (1974)

  27. Tettamanti, G., Morgan, I. G., Gombos, G., Vincendon, G., Mandel, P.: Subsynaptosomal localization of brain particulate neuraminidase. Brain Res.47, 515–518 (1972)

  28. Tettamanti, G., Preti, A., Lombardo, A., Bonali, F., Zambotti, V.: Parallelism of subcellular location of major particulate neuraminidase and gangliosides in rabbit brain cortex. Biochim. Biophys. Acta306, 466–477 (1973)

  29. Vaccari, A., Vertua, R., Furlani, A.: Decreased calcium uptake by rat fundal strips after pretreatment with neuraminidase or LSD in vitro. Biochem. Pharmacol.20, 2603–2612 (1971)

  30. Warren, L.: The thiobarbituric acid assay of sialic acids. J. Biol. Chem.234, 1971–1975 (1959)

  31. Whittaker, V. P.: Some properties of synaptic membranes isolated from the central nervous system. Ann. N. Y. Acad. Sci.137, 982–998 (1966)

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Correspondence to D. H. Hinzen.

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Hipp, F.X., Gielen, W., Davies, M.A. et al. Blocking action of intracellularly injected neuraminidase on central synapses in vivo. Pflügers Arch. 385, 45–50 (1980). https://doi.org/10.1007/BF00583914

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Key words

  • Neuraminidase
  • Synaptic transmission failure
  • Enzymatic microdissection