Abstract
Most of the brain glycogen, a major energy reserve that can be mobilized in response to increased neuronal activity, resides in the astrocyte, the site of the neuropathological abnormality found in hepatic encephalopathy (HE). Ammonia, a neurotoxin implicated in the pathogenesis of HE, has been reported to cause a depletion of glycogen in primary astrocyte cultures. To further investigate the action of ammonia on glycogen levels, cultured astrocytes were exposed to ammonium chloride (1–5 mM) for various times up to 7 d. Treatment with ammonia for 24 h did not alter deoxyglucose uptake, but significantly lowered peak glycogen values (found at 1.5 h following feeding with medium containing 5.5 mM glucose) in a concentration-dependent manner. This inhibitory effect was not observed after longer exposure times to ammonia. Three day treatment of cells did, however, significantly reduce norepinephrine-stimulated glycogenolysis, an effect not seen after 1 d of ammonia treatment. Part of the neurotoxic action of long term ammonia exposure in humans and experimental animals may be to inhibit the breakdown of glycogen. The effect of ammonia on astrocyte glycogen synthesis and/or breakdown may disrupt glial neuronal signaling and thus play a role in the pathogenesis of HE.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams R. D. and Foley J. M. (1953) The neurological disorder associated with liver disease.Assoc. Res. Nerv. Ment. Dis. Proc. 32, 198–237.
Bessman S. P. and Bessman A. N. (1955) The cerebral and peripheral uptake of ammonia in liver disease with a hypothesis for the mechanism of hepatic coma.J. Clin. Invest. 34, 622–628.
Butterworth R. F. and Giguere J. R. (1984) Region-selective glutamine changes in the CNS in relation to function in experimental subacute hepatic encephalopathy, inAdvances in Hepatic Encephalopathy and Urea Cycle Disease (Kleinberger, G., Ferenci P., Riederer P., and Thaler H., eds.), pp. 394–401, Karger, Basel, Switzerland.
Cambray-Deakin M., Pearce B., Morrow C. and Murphy S. (1988) Effects of neurotransmitters on astrocyte glycogen stores in vitro.J. Neurochem. 51, 1852–1857.
Cataldo A. M. and Broadwell R. D. (1986) Cytochemical identification of cerebral glycogen and glucose-6 phosphatase activity under normal and experimental conditions. I. Neurons and glia.J. Electron Microscop. Techn. 3, 413–437.
Cavanagh J. P. and Kyu N. H. (1971) Type II Alzheimer change experimentally produced in astrocytes in the rat.J. Neurol. Sci. 12, 63–75.
Dombro R. S., Lomako J., Lomako W. M., Whelan W., Hutson D. G., Blicharska J., Neary J. T., and Norenberg M. D. (1991) The action of ammonia on astrocyte glycogen levels.Trans. Am. Soc. Neurochem. 22, 132.
Fitzpatrick S. M., Cooper A. J., and Hertz L. (1988) Effects of ammonia and β-methylene-DL-aspartate on the oxidation of glucose and pyruvate by neurons and astrocytes in primary culture.J. Neurochem. 5, 1197–1203.
Gregorios J. B., Mozes L. W., Norenberg L.-O. B., and Norenberg M. D. (1985) Morphologic effects of ammonia on primary astrocyte cultures. I. Light microscopic studies.J. Neuropathol. Exp. Neurol. 44, 397–403.
Guth L. and Watson P. K. (1968) A correlated histochemical and quantitative study on cerebral glycogen after brain injury in the rat.Exp. Neurol. 22, 590–602.
Hawkins R. A., Miller A. L., Nielsen R. C., and Veech R. L. (1973) The acute action of ammonia on rat brain metabolism in vivo.Biochem. J. 134, 1001–1008.
Hindfelt B. and Siesjo B. K. (1971) Cerebral effects of acute ammonia intoxication. II. The effect upon energy metabolism.Scand. J. Clin. Lab. Invest. 28, 365–374.
Hindfelt B., Plum F., and Duffy T. E. (1977) Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts.J. Clin. Invest. 59, 386–396.
Ibrahim M. Z. M. (1975) Glycogen and its related enzymes of metabolism in the central nervous system.Adv. Anat. Embryol. Cell Biol. 52, 1–85.
Lai J. C., Murthy C. R., Cooper A. J., Hertz E., and Hertz L. (1989) Differential effects of ammonia and β-methylene-DL-aspartate on metabolism of glutamate and related amino acids by astrocytes and neurons in primary culture.Neurochem. Res. 14, 377–389.
Liskowsky D. R., Norenberg L.-O. B., and Norenberg M. D. (1986) Effect of ammonia on cyclic AMP production in primary astrocyte cultures.Brain Res. 386, 386–388.
Lomako J., Lomako W. M., Whelan W. J., Dombro R., Neary J. T., and Norenberg M. D. (1991) Glycogen biogenesis in rat-brain astrocyte.FASEB J. 5, A1014.
Lowry O. H., Rosebrogh N. J., Farr A. L., and Randall R. J. (1951) Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193, 265–275.
Lust W. D., Passoneau J. V., and Crites S. K. (1975) The measurement of glycogen in tissues by amylo-α-1,4-α-1,6-glucosidase after the destruction of preexisting glucose.Anal. Biochem. 68, 328–331.
Mossakowski M. J., Renkawek K., Krasnicka Z., Smialek M., and Pronaszko A. (1970) Morphology and histochemistry of Wilsonian and hepatogenic gliopathy in tissue culture.Acta Neuropathol. (Berl) 16, 1–16.
Nahorski S. R., Rogers K. J., and Edwards C. (1975) Cerebral glycogenolysis and stimulation of β-adrenoreceptors and histamine H2 receptors.Brain Res. 92, 529–533.
Neary J. T., Norenberg L.-O. B., Guitterez M. P., and Norenberg M. D. (1987) Hyperammonenmia causes altered protein phosphorylation in astrocytes.Brain Res. 437, 161–164.
Norenberg M. D. (1977) A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy.Lab. Investigation 36, 618–629.
Norenberg M. D. (1981) The astrocyte in liver disease.Adv. Cell Neurobiol. 2, 303–351.
Norenberg M. D. (1987) The role of astrocytes in hepatic encephalopathy.Neurochem. Pathol. 6, 13–33.
Norenberg M. D., Lapham L. W., Nichols F. A., and May A. G. (1974) An experimental model for the study of hepatic encephalopathy.Arch Neurol. 31, 106–109.
Raabe W. and Lin S. (1984) Ammonia, postsynaptic inhibition and CNS energy state.Brain Res. 303, 67–76.
Stalmans W., Bollen M., and Mvumbi L. (1987) Control of gycogen synthesis in health and disease.Diab. Metab. Rev. 3, 127–261.
Stone E. A. and Ariano M. A. (1989) Are glial cells targets of the central noradregenic system? A review of the evidence.Brain Res. Rev. 14, 297–309.
Subbarao K. V. and Hertz L. (1990) Effect of adrenergic angonists on glycogenolysis in primary cultures of astrocytes.Brain Res. 536, 220–226.
Swanson R. A., Yu A. C. H., Demediuk P., Sharp F. R., and Chan P. H. (1989) Ammonia causes depletion of glycogen in primary astrocyte culture.J. Neurochem. 52, S132.
Watanabe H. and Passoneau J. M. (1973) Factors affecting the turnover of cerebral glycogen and limit dextrin in vivo.J. Neurochem. 20, 1543–1554.
Zamora A. J., Cavanagh J. B., and Kyu M. H. (1973) Ultrastructural responses of the astrocytes to portocaval anastomosis in the rat.J. Neurol. Sci. 18, 25–45.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dombro, R.S., Hutson, D.G. & Norenberg, M.D. The action of ammonia on astrocyte glycogen and glycogenolysis. Molecular and Chemical Neuropathology 19, 259–268 (1993). https://doi.org/10.1007/BF03160004
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03160004