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Functional relationship between ammonia and gangliosides in brain

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Abstract

The functional significance of ammonia production in brain under physiological or pathological conditions is not clearly known. NH4 + stimulates Na+, K+ activated ATPase causing stabilization of neuronal membranes of which gangliosides are major structural components. Moreover ammonia is known to inhibit lysosomal enzymes which include enzymes degrading gangliosides. Gangliosides have been shown to stimulate neuritogenesis in neuronal cultures and prevent the damage of the neurons from glutamate toxicity particularly in areas of brain ischemia. Hyperammonemia without any behavioural changes was induced in experimental rats by intraperitoneal administration of either a single dose (0.8 mmol/100 g wt.) or by six ‘hourly’ doses (0.6 mmol/100 g wt.) of ammonium acetate. An increase in the content of gangliosides along with a rise in the content of GD1A and GD1B without any change in β-galactosidase and N-acetylhexosaminidase was observed in cerebral cortex, cerebellum, and brain stem, following the administration of single dose of ammonium acetate. Gangliosides, after extraction from the different brain regions, were estimated by the thiobarbituric acid method and expressed in terms of sialic acid. Individual gangliosides were separated and estimated by thin layer chromatography using resorcinol as the staining agent. These results suggest that ammonia production in the neuronal pathways in brain either as a result of repeated stimulation under physiological conditions or as a result of focal ischemia or injury, may likewise cause an increase in the content of gangliosides which may help in neuritic growth (physiological conditions facilitating synaptic plasticity) and may exert a protective effect on the neurons in the ischemic area against glutamate toxicity.

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References

  1. Aminoff, D. 1961. Method for the quantitative estimation of N-acetalyneuraminic acid and their application to hydrolysates of sialic acid mucoids. Biochem. J. 81:304–312.

    Google Scholar 

  2. Benzamin, A. M. 1982. Ammonia. Pages 117–137,in A. Lajtha, (ed.) Hand book of Neurochemistry Vol. 1, (2nd ed) New York, Plenum.

    Google Scholar 

  3. Bessman, S. P., and Pal, N. 1976. The Krebs cycle depletion theory of hepatic coma. Pages 83–89in Grisolia, S., Baguena, R., and Mayor, F. (eds.) the urea cycle: John Wiley, New York.

    Google Scholar 

  4. Byrno, M. C., Ledeen, R. W., Roisen, F. J., York, G., and Salefam, J. R. 1983. Ganglioside induce neuritogenesis, verification that gangliosides are the active agents and the comparison of molecular species. J. Neurochem. 41:1214–1222.

    PubMed  Google Scholar 

  5. Cavanagh, J. B., and Kyw, M. W. 1971. Type II Alzheimer change experimentally produced in astrocytes in rat. J. Neurol. Sci. 12:63–75.

    PubMed  Google Scholar 

  6. Chambon, P., Ramuz, M., Mandel, P., and Doly, J. 1968. The influence of ionic strength and a polyanion on transcription in vitro. I. Stimulation of the aggregate RNA polymerase from rat liver nuclei. Biochem. Biophys. Acta. 157:504–519.

    Google Scholar 

  7. Chombon, P., Karon, H., Ramuz, M., and Mendel, P. 1968. The influence of ionic strength and a polyanion on transcription in vitro. II. Effects on the template efficiency of rat liver chromatin for a purified bacterial RNA polymerase. Biochem. Biophys. Acta. 157:520–531.

    PubMed  Google Scholar 

  8. Cooper, A. J. L., and Plum, F. 1987. Biochemistry and physiology of brain ammonia. Physiol. Rev. 67:440–519.

    PubMed  Google Scholar 

  9. Correa, S. G., Birnco, I. D., Riera, C. M., and Fiedelio, B. D. 1991. Anti-inflammatory effect of gangliosides in the rat hind paw oedema test. Eur. J. Pharmacal. 199:93–98.

    Google Scholar 

  10. Feveron, M., Maney, H., Alho, H., Bertilino, M., Ferret, B., Guidotti, A., and Costs A. 1988. Gangliosides prevent glutamate and kainate neuro toxicity in primary neuronal cultures of neonatal rat cerebellum and cortex. Proc. Natl. Acad. Sci. U.S.A. 8:7351–7355.

    Google Scholar 

  11. Fischer, J. E., and Baldassarin, R. J. 1976. Pathogenesis and therapy of hepatic coma. Progress. Liver Dis. 5:363–397.

    Google Scholar 

  12. Gatt, S. 1969. Betagalactosidase from rat brain., Methods in Enzymology. (J. M. Lowenstein (eds.)). New York Academic Press XIV, 156–161.

    Google Scholar 

  13. Ghori, M. I., Subramanyam, K., Moorthy, B., and Sadasivudu, B. 1985. Functional relationship of ammonia with RNA, DNA and protein in rat muscle, B.: Biochem. Med. 33:284–290.

    Google Scholar 

  14. Hawkins, R. A., Miller, A. L., Nielson, R. C., and Veech, R. L. 1973. The acute action of ammonia on rat brain metabolism in vivo. Biochem. J. 134:1001–1008.

    PubMed  Google Scholar 

  15. Hindfelt, B., Plum, F., and Duffy, T. E. 1977. Effect of acute ammonia intoxication of cerebral metabolism in rats with portocaval shunts. J. Clin. Invest. 59:386–396.

    PubMed  Google Scholar 

  16. Irwin, C. C., and Irwin, L. N. 1979. A single, rapid method for ganglioside isolation from small amounts of tissue. Analytical Biochem. 94:335–339.

    Google Scholar 

  17. Ivorsmith, and Seakins, J. W. T. 1976. Chromatographic and electrophoretic techniques. Vol. 1, London, William Heinemann.

    Google Scholar 

  18. Levy, G. A., and Conchie, J. 1966. Mammalian glycosidases and their inhibition by aldonolactones. Methods in enzymology, New York, Academic Press VIII, 577–580.

    Google Scholar 

  19. Meldrum, B. S., and Garthwaite, J. 1990. Excitatory aminoacid neurotoxicity and neurodegenerative disease. Trends., Pharmacol. Sci. II, 379–398.

    Google Scholar 

  20. McIlwain, H., and Bachelord, H. S. 1985. Biochemistry and central nervous system, London, Churchill.

  21. Parker, T. H., Roberts, R. K., Vorhees, C. V., Schmidt, D. E., and Schenker, S. 1977. The effect of acute and subacute ammonia intoxication on regional cerebral acetyl choline levels in rat. Biochem. Med. 18:235–244.

    PubMed  Google Scholar 

  22. Rothman, S. M., and Olney, J. W. 1986. Glutamate and pathophysiology of hypoxic-ischaemic brain damage. Ann. Neurol. 19:105–11.

    PubMed  Google Scholar 

  23. Sadasivudu, B., and Lajtha, A. 1970. Metabolism of aminoacids in incubated slices of mouse brain. J. Neurochem. 17:1299–1311.

    PubMed  Google Scholar 

  24. Sadasivudu, B., and Rao, T. I. 1976. Studies on functional and metabolic role of urea cycle intermediates in brain. J. Neurochem. 27:785–795.

    PubMed  Google Scholar 

  25. Sadasivudu, B., Rao, T. I., and Murthy, C. R. K. 1977. Acute metabolic effects of ammonia in mouse brain. Neurochem. Res. 2:639–665.

    Google Scholar 

  26. Sadasivudu, B., and Murthy, C. R. K. 1978. Effects of ammonia on monoamine oxidase and enzyme of GABA metabolism in mouse brain. Arch. Physiol. Biochem. 86:67–82.

    Google Scholar 

  27. Sadasivudu, B., Rao, T. I., and Murthy, C. R. K. 1979. Chronic metabolic effects of ammonia in mouse brain. Arch. Int. Physical. Biochem. 87:871–885.

    Google Scholar 

  28. Sadasivudu, B., Murthy, C. R. K., Rao, G. N., and Swamy, M. 1982. Studies on acetylcholine esterase & gammaglutamyl transpeptidase in mouse brain in ammonia toxicity. J. Neuro. Sci. Res. 9:127–134.

    Google Scholar 

  29. Schenker, S., and Mendelson, J. H. 1964. Cerebral adenosine triphosphate in rats with ammonia induced coma. Am. J. Physiol. 206:1173–1176.

    PubMed  Google Scholar 

  30. Seglen, P. O., and Reith, A. 1976. Ammonia inhibition of protein degradation in isolated rat hepatocytes. Quantitative ultrastructural alterations in the lysosomal system. Exptl. Cell. Res. 100:276–280.

    PubMed  Google Scholar 

  31. Subbalakshmi, G. Y. C. V., and Murthy, C. R. K. 1981. Effects of methionine sulfoxamine on rat cerebral protein. Baroda J., Nut. 8:63–66.

    Google Scholar 

  32. Subramanyam, K., Prasad, M. S. K., Rangavalli, G., Muralidhar, K., and Sadasivudu, B. 1985. Functional relationship of ammonia to DNA, RNA and protein in brain. Neuroscience, 15:887–890.

    PubMed  Google Scholar 

  33. Svennerholm, I. 1963. Chromatographic separation of human brain gangliosides. J. Neurochem. 10:613–623.

    PubMed  Google Scholar 

  34. Tsukada, Y. 1971. Ammonia Metabolism. In hand book of Neurochemistry (Ed. Lajtha, A.) Vol. 5, Part A pp 215–232, Plenum Press, New York.

    Google Scholar 

  35. Valdimirova, E. A. 1954. Ammonia formation in rat cerebellum hemispheres induced by conditional stimuli. Doki, Akad, Nauk, SSSR XCV 905–908.

    Google Scholar 

  36. Vladimir, P. Skipki. 1975. TLC of neural glycosphingolipid, Methods of Enzymology. XXXV Part B, New York, Academic Press 396–425.

    Google Scholar 

  37. Walker, C. O., Speeg, K. V. K., Levinson, J. D., and Schenker, S. 1971. Cerebral acetylcholine, serotonin and norepinephrine in acute ammonia toxication. Proc. Soc. Exp. Biol. Med. 136:668–671.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, M.R. Medical College, 585 105, Gulbarga, (Karnataka State), India

    B. Sadasivudu (Head)

  2. Biochemistry Department, Osmania Medical College, Hyderabad, India

    Prabha Modi (Assistant Professor)

  3. Department of Biochemistry, Kempegowda Medical College, Bangalore, India

    U. Lakshminarayana (Professor and Head)

  4. Department of Life Sciences, Central University, Hyderabad, India

    C. R. K. Murthy

Authors
  1. Prabha Modi
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  2. B. Sadasivudu
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  3. U. Lakshminarayana
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  4. C. R. K. Murthy
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Former Professor of Biochemistry, OMC, Hyderabad.

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Modi, P., Sadasivudu, B., Lakshminarayana, U. et al. Functional relationship between ammonia and gangliosides in brain. Neurochem Res 19, 353–358 (1994). https://doi.org/10.1007/BF00971585

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