Summary
Activities of glutamic acid decarboxylase (GAD), glutamine synthetase (GS), glutamate dehydrogenase (GDH) and α-ketoglutarate dehydrogenase (αKGDH) were measured in autopsied brain tissue from nine cirrhotic patients dying in hepatic coma and an equal number of appropriately-matched control patients who were free from hepatic, neurological or psychiatric diseases in all cases. Activities of GAD were unchanged in cirrhotic brain tissue suggesting no loss of integrity of presynaptic GABA nerve terminals in this disease. Similarly, activities of the mitochondrial enzyme αKGDH were within normal limits in brain tissue from cirrhotic patients. On the other hand GS and GDH activities were selectively decreased by 20–30% in caudate nuclei of these patients. Previous immunocytochemical studies suggest that both GS and GDH are enriched in astrocytes. Thus, loss of these enzymes is consistent with the marked Alzheimer type II astrocytosis characteristic of hepatic encephalopathy resulting from chronic liver disease and shown to be particularly severe in caudate nucleus. Selective loss of glial GDH activity in these brains could result in abnormalities of glutamatergic function in this disease.
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References
Aoki C., Milner T.A., Sheu K.F.R., Blass J.P. and Pickel V.M. (1987). Regional distribution of astrocytes with intense immunoreactivity for glutamate dehydrogenase in rat brain: implications for neuron-glia interactions in glutamate transmission. J. Neurosci. 7, 2214–2231.
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.
Butterworth R.F. (1986). Cerebral thiamine-dependent enzyme changes in experimental Wernicke’s Encephalopathy. Metab. Brain Dis. vol. 1, no. 3, 167–175.
Butterworth R.F., Giguère J.F. and Besnard A.M. (1986). Actitivities of thiamino-dependent enzyme changes in two experimental models of thiamine-deficiency encephalopathy. 2. α-ketoglutarate dehydrogenase. Neurochem. Res. vol. 11, no. 4, 567–577.
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.
Butterworth R.F., Girard G. and Giguère J.F. (1988a). Regional differences in the capacity for ammonia removal following portacaval anastomosis in the rat. J. Neurochem. 51, 486–490.
Butterworth R.F., Lavoie J., Giguère, J.F. and Pomier Layrargues G. (1988b). Affinities and densities of high-affinity [3H]-muscimol (GABA-A) binding sites and of central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Hepatoloqy, 8, 1084–1088.
Butterworth R.F. (1989). Effects of thiamine deficiency on brain metabolism: implications for the pathogenesis of the Wernicke-Korsakoff Syndrome. Alcohol & Alcoholism, (in press).
Carter C.J. (1982). Loss of glutamine synthetase activity in the brain in Hungtington’s Disease. The Lancet, 1, 782–783.
Cooper A.J.L. and Plum F. (1987). Biochemistry and physiology of brain ammonia. Physiol. Rev. 67, 440–519.
Filia A., De Michele G., Brescia Morra V., Palma V., Di Lauro A., Di Geronimo G. and Campanella G. (1986). Glutamate dehydrogenase: human brain in regional distribution and properties. J. Neurochem, 46, 422–424.
Giguère J.F. and Butterworth R.F. (1984). Amino acid changes in relation to function in experimental portal-systemic encephalopathy. Neurochem. Res. vol. 9, no. 9, 1309–1321.
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.
Kisfaludy S. (1975). Effects of ammonia intoxication and liver injury on rat brain glutamate dehydrogenase and glutaminase activity. Acta Medica Acad. Sci. Hung. 32 279–287.
Lavoie J., Giguère J.F., Pomier Layrargues G. and Butterworth R.F. (1987a). Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J. Neurochem. 49, 692–697.
Lavoie J., Giguère J.F., Pomier Layrargues G. and Butterworth, R.F. (1987b). Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy. Metabolic Brain Disease, 2, 283–290.
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., 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.
Rothstein J.D. and Tabakoff B. (1984). Alteration of striatal glutamate release after glutamine synthetase inhibition. J. Neurochem 43, 1438–1446.
Schafer D.F. and Jones E.A. (1982). Hepatic encephalopathy and the Math-aminobutyric acid neurotransmitter system. The Lancet 1, 18–20.
Wenthold R.J., Altschuler R.A., Skaggs K.K. and Reeks K.A. (1987). Immunocytochemical characterization of glutamate dehydrogenase in the cerebellum of the rat. J. Neurochem. 48, 636–643.
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Giguère, JF., Besnard, AM., Lavoie, J., Layrargues, G.P., Butterworth, R.F. (1989). Activities of Giutamate-Related Enzymes in Autopsied Brain Tissue from Cirrhotic Patients with Hepatic Encephalopathy. In: Butterworth, R.F., Layrargues, G.P. (eds) Hepatic Encephalopathy. Experimental Biology and Medicine, vol 22. Humana Press. https://doi.org/10.1007/978-1-4612-4506-3_30
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DOI: https://doi.org/10.1007/978-1-4612-4506-3_30
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