Abstract
The metabolism of GABA and other amino acids was studied in the substantia nigra, the hippocampus and the parietal cortex of rats following microinjections of GAMMA-vinyl-GABA during status epilepticus induced by lithium and pilocarpine. GABA metabolism showed striking regional variations. In controls, both GABA concentration and rate of GABA synthesis were highest in the substantia nigra and lowest in cortex, as expected. In substantia nigra, status epilepticus resulted in a 2 1/2 fold decline in the rate of GABA synthesis and in a 307% increase in the turnover time of the GABA pool. In hippocampus, the rate of GABA synthesis was not altered significantly, but the turnover time of the GABA pool was 284% of controls, and the size of that pool increased to 208% of controls. By contrast, in cortex, where seizure activity is limited in this model, the rate of GABA synthesis increased to 230% of controls while pool size and turnover time did not change. Aspartate concentration decreased in all three brain regions. These data suggest that the observed reduction of the rate of GABA synthesis in substantia nigra could play a key role in seizure spread in this model of status epilepticus.
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Roberts, E., Baxter, C. F., Van Harreveld, A., Wiersman, C. A. G., Adey, W. R., and Killiam, K. F. (eds). 1960. Inhibition in the Nervous system and Gamma Amino Butyric Acid.
Krnjevic, K. 1983. GABA mediated inhibitory mechanisms in relation to epileptic discharges. Pages 249–280,in Jasper, H. H. and Van Gelder, N. M. (eds.), Basic Mechanisms of Neuronal Excitability, Alan R. Liss, New York.
Wasterlain, C. G., Morin, A. M., and Dwyer, B. E. 1985. The Epilepsies. Pages 319–419,in A. Lajtha (ed), Handbook of Neurochemistry, Vol 10, Pathological neurochemistry, Raven Press, New York.
Coursin, D. B. 1954. Convulsive seizures in infants with pyridoxine-deficient diet. J. Am. Med. Assoc. 154:406–408.
Tower, D. B. 1956. Symposium on role of some newer vitamins in human metabolism and nutrition; neurochemical aspects of pyridoxine metabolism and function. Am. J. Clinic Nutr. 4:329–345.
Bain, J. A., and Williams, H. L. 1960. Pages 275–293,in Roberts, E., Baxter, C. G., Van Harreveld, A., Wiersman, C. A. G., Adey, W. R. (eds), Inhibition in the Nervous System and Gamma amino butyric acid.
Davenport, V. D., and Davenport, H. W. 1948. Brain excitability in pyridoxine-deficient rats. J. Nutr. 36:263–276.
Cutis, D. R., Ruggan, A. W., Felix, D., and Johnston, G. A. R. 1971. Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Res. 32:69–96.
Hayashi, T. 1959. The inhibition of β-hydroxy-gamma-aminobutyric acid upon the seizure following stimulation of the motor cortex of the dog. J. Physiol. (London) 145:570–578.
Gale, K., and Iadarola, M. J. 1980. Seizure protection and increased nerve terminal GABA: delayed effects of GABA transaminase inhibition. Science 208:288–289.
Iadarola, M. J., and Gale, K. 1982. Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid. Science 218:1237–1240.
Gale, K. 1984. The role of the substantia nigra in the anticonvulsant actions of GABAergic drugs Pages 57–79,in Fariello, R. G., Lloyd, K., Morselli, P. L., Quesney, L. F., and Engle, J. Jr. (eds), Neurotransmitters, Seizures and Epilepsy II Raven Press, New York.
Delgado-Escueta, A. V., Wasterlain, C. G., Treiman, D., and Porter (eds). 1983. Status Epilepticus: Mechanisms of brain damage and treatment, 578 pages. Raven Press, New York.
Wasterlain, C. G., Fujikawa, D. G., Penix, L., Sankar, R. 1992. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia (in press).
Wasterlain, C. G., Lockwood, A. H., and Conn, M. 1978. Chronic inhibition of brain protein synthesis after portacaval shunting: A possible pathogenic mechanism in chornic hepatic encephalopathy in the rat. Neurology 28:233–238.
Wasterlain, C. G. 1974. Mortality and morbidity from serial seizures: An experimental study. Epilepsia 15:155–176.
Wasterlain, C. G. 1977. Effects of epileptic seizures on brain ribosomes: Mechanism and relationship to cerebral energy metabolism. J. Neurochem. 29:707–716.
Wasterlain, C. G., Bronstein, J. M., Morin, A. M., Dwyer, B. E., and Sankar, R. 1992. Translocation and autophosphorylation of brain calmodulin kinase II in status epilepticus,in Engel, Jr., J., Wasterlain, C. G., Cavalheiro, E., Heinemann, E., and Avanzini, G. (eds), Molecular Neurobiology and Epilepsy. Elsevier, Amsterdam. (in press).
Baxter, C. F., Wasterlain, C. G., Oh, C. C., and Baldwin, R. A. 1991 Postictal changes in GABA metabolism in substantia nigra. Soc. Neurosci. Abst. 17:596.
Baxter, C. F., Parsons, J. E., Oh, C. C., Wasterlain C. G. and Baldwin, R. A. 1989. Changes of amino acid gradients in brain tissue induced by microwave irradiation and other means. Neurochem. Res. 14:909–913.
Baxter, C. F., Oh, C. C., Wasterlain, C. G., Ozaki, L. K., and Baldwin, R. A. 1991. Alterations of GABA metabolism and seizure susceptibility in the substantia nigra of the kindled rat acclimating to changes in osmotic state. Neurochem. Res. 16:269–278.
Paxinos, G., and Watson, C. 1986. The Rat Brain in Sterotaxic Coordinates, Second edition. Academic Press, New York.
Smith, P. K., Krohn, R. I., Hermanson, G. T., Nalia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. N., Olson, B. J., and Klenk, D. C. 1985. Measurement of protein using bicinchoninic acid. Analyt. Biochem. 150:76–85.
Baxter, C. F., Wasterlain, C. G., Hallden, K. L., and Pruess, P. 1986. Effect of altered blood plasma osmolalities on regional brain amino acid concentrations and focal seizure susceptibility in the rat. J. Neurochem. 47:617–624.
Fujikawa, D. G. The temporal profile and regional distribution of neuronal necrosis from pilocarpine seizures. J. Neurosci. (In press).
Arias, C., Nontiel, T., and Tapia, R. 1990. Transmitter release in hippocampal slices from rats with limbic seizures produced by systemic administration of kainic acid. Neurochem. Res. 15:641–645.
Abdul-Ghini, A. S., Ghneim, H., el-Lati, S., and Saca'an, S. 1989. A change in the activity of glutamate related enzymes in cerebral cortex, during insulin-induced seizures. Int. J. Neurosci. 44:67–74.
Koyama, I. 1972. Amino acids in the cobalt-induced epileptogenic and nonepileptogenic cat's cortex. Can. J. Physiol. Pharmacol. 50:740–752.
Emson, P. C., Joseph, N. H. 1975. Neurochemical and morphological changes during the development of the cobalt-induced epilepsy in the rat. Brain Res. 93:91–110.
van Gelder, N. M., and Courtois, A. 1972. Close correlation between changing content of specific amino acids in epileptogenic cortex of rats, and severity of epilepsy. Brain Res. 43:477–484.
van Gelder, N. M. 1972. Antagonism by taurine of cobalt induced epilepsy in cat and mouse. Brain Res. 47:157–165.
Craig, C. R., and Hartman, E. R. 1973. Concentration of amino acids in the brain of cobalt-epileptic rat. Epilepsia 14:409–414.
Cavalheiro, E. A., Fernandes, N. J., Turski L., and Mazzacoratti, M. G. M. 1992. Neurochemical changes in the hippocampus of rats with spontaneous recurrent seizures.in J. Engle, Jr., C. G. Wasterlain, E. Cavalheiro, E. heinemann, G. Avanzini, (eds), Molecular Neurobiology and Epilepsy. Elsevier Amsterdam. In press.
Maggio, R., and Gale, K. 1989. Seizures evoked from area tempestas are subject to control by GABA and glutamate receptors in substantia nigra. Exp. Neurol. 105:184–188.
McNamara, J. O. 1978. Selective alterations of regional beta-adrenergic receptor binding in the kindling model of epilepsy. Exp. Neurol. 61:582–591.
King, L. J., Carl, J. L., and Lao, L. 1973. Carbohydrate metabolism in brain during convulsions and its modification by phenobarbitone. J. Neurochem. 20:477–485.
Nahorski, S. R., Roberts, D. J., and Stewart, G. G. 1970. Some neurochemical aspects of pentamethylenetetrazole convulsive activity in rat brain. J. Neurochem. 17:621–631.
Chapman, A. G., Meldrum, B. S., and Siesjo, B. K. 1977. Cerebral metabolic changes during prolonged epileptic seizures in rats. J. Neurochem. 28:1025–1035.
Blennow, G., Folbergrova, J., Nilsson, B., and Siesjo, B. K. 1979. Effects of bicuculline-induced seizures on cerebral metabolism and circulation of rats rendered hypoglycemic by starvation. Ann. Neurol. 5:139–151.
Howse, D. C., and Duffy, T. E. 1975. Control of the redox state of the pyridine nucleotides in the rat cerebral cortex. Effect of electroshock-induced seizures. J. Neurochem. 24:935–940.
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Wasterlain, C.G., Baxter, C.F. & Baldwin, R.A. GABA metabolism in the substantia nigra, cortex, and hippocampus during status epilepticus. Neurochem Res 18, 527–532 (1993). https://doi.org/10.1007/BF00967257
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DOI: https://doi.org/10.1007/BF00967257