Abstract
Activities of the γ-aminobutyric acid (GABA) and cholinergic nerve-terminal marker enzymes glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) as well as the astrocytic enzyme glutamine synthetase (GS) were measured in homogenates of dissected brain tissue obtained at autopsy from nine cirrhotic patients dying in hepatic encephalopathy and an equal number of control subjects matched for age, agonal status, and time interval from death to freezing of autopsied material. GAD activities varied as a function of agonal status in control samples, confirming a previous report, but were unchanged in brain tissue from cirrhotic patients, suggesting no loss of integrity of presynaptic GABA nerve terminals in this disease. On the other hand, GS activities were selectively decreased by 25% (P < 0.01) in caudate nuclei of cirrhotic patients, reflecting, no doubt, the severe astrocytosis consistently observed in this brain structure. CAT activities, expressed per milligram of protein, were found to be increased by 30% (P < 0.01) in the prefrontal cortex of cirrhotic patients. Whether such changes result from a relative increase in CAT as a consequence of losses of astrocytic protein or reflect altered cholinergic function in hepatic encephalopathy associated with chronic liver disease awaits further study.
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. In Merritt, H. H., and Hare, C. C. (eds.),Metabolic and Toxic Diseases of the Nervous System, Williams and Wilkins, Baltimore, pp. 198–237.
Bird, E. D., and Iversen, L. L. (1974). Huntington's chorea: Postmortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia.Brain 97: 457–472.
Bowen, D. M., Smith, C. B., White, P., and Davison, A. N. (1976). Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies.Brain 99: 459–496.
Butterworth, R. F., and Giguère, J. F. (1986). Cerebral amino acids in portal-systemic encephalopathy: Lack of evidence for altered γ-aminobutyric acid (GABA) function.Metab. Brain Dis. 1: 221–228.
Butterworth, R. F., Giguère, J. F., Michaud, J., Lavoie, J., and Pomier Layrargues, G. (1987a). Ammonia: Key factor in the pathogenesis of hepatic encephalopathy.Neurochem. Pathol. 6: 1–12.
Butterworth, R. F., Lavoie, J., Giguère, J. F., Pomier Layrargues, G., and Bergeron, M. (1987b). Cerebral GABAergic and glutamatergic function in hepatic encephalopathy.Neurochem. Pathol. 6: 131–144.
Carter, C. J. (1982). Loss of glutamine synthetase activity in the brain of Huntington's disease.Lancet 1: 782–783.
Cooper, A. J. L., and Plum, F. (1987). Biochemistry and physiology of brain ammonia.Physiol. Rev. 67: 440–519.
De Armond, S. J., Fusco, M. M., and Dewey, M. M. (1976).Structure of the Human Brain: A Photographic Atlas, 2nd ed., Oxford University Press, New York
Fonnum, F. (1975). A rapid radiochemical method for the determination of choline acetyltransferase.J. Neurochem. 24: 407–409.
Giguère, J. F., and Butterworth, R. F. (1982). Glutamic acid abnormalities in the central nervous system in hepatic encephalopathy.Clin. Biochem. 15: 95.
Gutierrez, J. A., and Norenberg, M. D. (1977). Ultrastructural study of methionine sulfoximine-induced Alzheimer type II astrocytosis.Am. J. Pathol. 86: 285–300.
Hindfelt, B., Plum, F., and Duffy, T. E. (1977). Effect of acute ammonia intoxication on cerebral metabolism in rats with portocaval shunts.J. Clin. Invest. 59: 386–396.
Lavoie, J., Giguère, J. F., Pomier Layrargues, G., and Butterworth, R. F. (1987). Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy.J. Neurochem. 49: 692–697.
McGeer, P. L., and McGeer, E. G. (1976). Enzymes associated with the metabolism of catecholamines, acetylcholine and GABA in human controls and patients with Parkinson's disease and Huntington's chorea.J. Neurochem. 26; 65–76.
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 acetylcholine levels in rats.Biochem. Med. 18: 235–244.
Patel, A. J., Hunt, A., and Tahourdin, C. S. M. (1983). Regional development of glutamine synthetase activity in the rat brain and its association with the differentiation of astrocytes.Dev. Brain Res. 8: 31–37.
Perry, E. K., and Perry, R. H. (1983). Human brain neurochemistry—some postmortem problems.Life Sci. 33: 1733–1743.
Perry, E. K., Gibson, P. H., Blessed, Cr., Perry, R. H., and Tomlinson, B. E. (1977). Neurotransmitter enzyme abnormalities in senile dementia.J. Neurol. Sci. 34: 247–265.
Record, C. O., Buxton, B., Chase, R. A., Curzon, G., Murray-Lyon, I. M., and Williams, R. (1976). Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy.Eur. J. Clin. Invest. 6: 387–394.
Ritchie, T., Scully, S. A., De Vellis, J., and Noble, E. P. (1986). Stability of neuronal and glial marker enzymes in postmortem rat brain.Neurochem. Res. 11: 383–392.
Rothstein, J. D., and Tabakoff, B. (1984). Alteration of striatal glutamate release after glutamine synthetase inhibition.J. Neurochem. 43: 1438–1446.
Roy, S., Pomier Layrargues, G., Butterworth, R. F., and Huet, P. M. (1987). Hepatic encephalopathy in cirrhotic and portocaval shunted dogs: Lack of changes in brain GABA uptake, brain GABA levels and brain glutamic acid decarboxylase activity.J. Hepatol. (in press).
Schafer, D. F., and Jones, E. A. (1982). Hepatic encephalopathy and the γ-aminobutyric acid neurotransmitter system.Lancet 1: 18–20.
Spokes, E. G. S., and Koch, D. J. (1978). Post-mortem stability of dopamine, glutamate decarboxylase and choline acetyltransferase in the mouse brain under conditions simulating the handling of human autopsy material.J. Neurochem. 31: 381–383.
van Gelder, N. M. (1974). Glutamate dehydrogenase, glutamic acid decarboxylase and GABA aminotransferase in epileptic mouse cortex.Can. J. Physiol. Pharmacol. 52: 952–959.
Zanchin, G., Maggioni, F., Salassa, D., and Vassanelli, P. (1984). GABA and dopamine receptors after chronic portacaval shunt in the rat. In Kleinberger, G., Ferenci, P., Riederer, P., and Thaler, H. (eds.),Advances in Hepatic Encephalopathy and Urea Cycle Enzymes, Karger, Basel, pp. 360–367.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lavoie, J., Giguère, J.F., Layrargues, G.P. et al. Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy. Metab Brain Dis 2, 283–290 (1987). https://doi.org/10.1007/BF00999698
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00999698