Neuroactive Amino Acids in Synaptosomes from Focal and Nonfocal Temporal Lobe Tissue of Patients with Intractable Complex Partial Seizures

  • P.-L. Lleu
  • D. Labiner
  • M. Weinand
  • R. J. Huxtable
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 359)


The putative involvement of disturbances in amino acid patterns in the pathogenesis of epilepsy has been vigorously debated (13,34,36,47,50). Amino acid levels in whole tissue removed from epileptic foci at surgery or autopsy have been compared with levels in surrounding nonfocal tissue or with tissue removed at autopsy or surgery from nonepileptic subjects. The advantages and disadvantages of each procedure have been argued at length (13,34,36,47,50). No clear pattern of changes has emerged, however (2,5,7,10,12,13,15,1–8,19,21,23,26,30,32,35,36,38,40,48,50). The literature on changes in amino acids in epilepsy has been reviewed (9,16).


Cobalt Glycine Cysteine Sulfuric Acid Glutamine 


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  1. 1.
    Almarghini, K., Remy, A., and Tappaz, M. 1991, Immunocytochemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase, in the cerebellum: Evidence for a glial localization, Neuroscience, 43:111–119.CrossRefGoogle Scholar
  2. 2.
    Avoli, M. 1991, Excitatory amino acid receptors in the human epileptogenic neocortex, Epilepsy Res. 10:33–40.CrossRefGoogle Scholar
  3. 3.
    Berl, S. and Clarke, D.D. 1978, Metabolic compartmentation of the glutamate-glutamine system: glial contribution, in: “Amino Acids as Chemical Transmitters”, Fonnum, F. ed., Plenum Press, New York, pp. 691–708.CrossRefGoogle Scholar
  4. 4.
    Bonhaus, D.W., Laird, H., Mimaki, T., Yamamura, H.I., and Huxtable, R.J. 1983, Possible bases for the anticonvulsant action of taurine, in: “Sulfur Amino Acids: Biochemical and Clinical Aspects”, Kuriyama, K., Huxtable, R.J. and Iwata, H. eds., A.R.Liss, New York, pp. 195–209.Google Scholar
  5. 5.
    Bonhaus, D.W., Lippincott, S.E., and Huxtable, R.J. 1984, Subcellular distribution of neuroactive amino acids in brains of genetically epileptic rats, Epilepsia, 25:564–568.CrossRefGoogle Scholar
  6. 6.
    Carl, G.F., Thompson, L.A., Williams, J.T., Wallace, V.C., and Gallagher, B.B. 1992, Comparison of glutamine synthetases from brains of genetically epilepsy prone and genetically epilepsy resistant rats, Neurochem.Res. 17:1015–1019.CrossRefGoogle Scholar
  7. 7.
    Craig, C.R. and Hartmann, E.R. 1973, Concentration of amino acids in the brain of cobalt epileptic rat, Epilepsia, 14:409–414.CrossRefGoogle Scholar
  8. 8.
    Dodd, P.R., Bradford, H.F., Abdul-Ghani, A.S., Cox, D.W.G., and Continho-Netto, J. 1980, Release of amino acids from chronic epileptic and sub-epileptic foci in vivo, Brain Res. 193:505–517.CrossRefGoogle Scholar
  9. 9.
    Emson, P.C. 1978, Biochemical and metabolic changes in epilepsy, in: “Taurine and Neurological Disorders”, Barbeau, A. and Huxtable, R.J. eds., Raven Press, New York, pp. 319–338.Google Scholar
  10. 10.
    Fumero, S. and Mondino, A. 1976, Longitudinal changes of brain amino acid content occurring before, during and after epileptic activity, Brain Res. 24:1–9.Google Scholar
  11. 11.
    Gray, E.G. and Whittaker, V.P. 1962, The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived by homogenization and centrifugation, J.Anat. 96:79–88.Google Scholar
  12. 12.
    Hamberger, A., Haglid, K., Nyström, B., and Silfvenius, H. 1993, Co-variation of free amino acids in human epileptogenic cortex, Neurochem.Res. 18:519–525.CrossRefGoogle Scholar
  13. 13.
    Hansen, S., Perry, T.L., Wada, J.A., and Sokol, M. 1973, Brain amino acids in baboons with light-induced epilepsy, Brain Res. 50:480–483.CrossRefGoogle Scholar
  14. 14.
    Hertz, L., Kvamme, E., McGeer, E.G., and Schousboe, A. 1984, “Glutamine, Glutamate, and GABA in the Central Nervous System”, Alan R. Liss, Inc. New York.Google Scholar
  15. 15.
    Hiramatsu, M., Edamatsu, R., Suzuki, S., Shimada, M., and Mori, A. 1990, Regional excitatory and inhibitory amino acid levels in epileptic El mouse brain, Neurochem.Res. 15:821–825.CrossRefGoogle Scholar
  16. 16.
    Huxtable, R.J. 1981, Insights on function: metabolism and pharmacology of taurine in the brain, in: “The Role of Peptides and Amino Acids as Neurotransmitters”, Lombardini, J.B. and Kenny, A. eds., A.R.Liss, New York, pp. 53–97.Google Scholar
  17. 17.
    Huxtable, R.J. 1989, Taurine in the central nervous system and the mammalian actions of taurine, Prog.Neurobiol. 32:471–533.CrossRefGoogle Scholar
  18. 18.
    Huxtable, R.J., Bonhaus, D., and Lehmann, A. 1986, Excitatory and inhibitory amino acids in the genetically seizure-susceptible rat, in: “Neurotransmitters in Epilepsy”, Nistico, G., Morselli, P., Lloyd, K.G., Fariello, R.G. and Engel, J. eds., Raven Press, New York, pp. 369–385.Google Scholar
  19. 19.
    Huxtable, R.J., Laird, H., Bonhaus, D., and Thies, A.C. 1982, Correlations between amino acid concentrations in brains of seizure-susceptible and seizure-resistant rats, Neurochem.International, 4:73–78.CrossRefGoogle Scholar
  20. 20.
    Huxtable, R.J., Laird, H., Lippincott, S.E., and Walson, P. 1983, Epilepsy and the concentrations of plasma amino acids in humans, Neurochem.International, 5:125–135.CrossRefGoogle Scholar
  21. 21.
    Huxtable, R.J. and Laird, H.E. 1978, Are amino acid patterns necessarily abnormal in epileptic brains? Studies on the genetically seizure-susceptible rat, Neuroscience Letters, 10:341–345.CrossRefGoogle Scholar
  22. 22.
    Janjua, N.A., Itano, T., Kugoh, T., Hosokawa, K., Nakano, M., Matsui, H., and Hatase, O. 1992, Familial increase in plasma glutamic acid in epilepsy, Epilepsy Res. 11:37–44.CrossRefGoogle Scholar
  23. 23.
    King, L.J., Carl, J.L., and Lao, L. 1974, Brain amino acids during convulsions, J.Neurochem. 22:307–309.CrossRefGoogle Scholar
  24. 24.
    Kontro, P. and Oja, S.S. 1987, Taurine and GABA release from mouse cerebral cortex slices: effects of structural analogues and drugs, Neurochem.Res. 12:475–482.CrossRefGoogle Scholar
  25. 25.
    Koyama, I. 1972, Amino acids in the cobalt induced epileptogenic and nonepileptogenic cat’s cortex, Can.J.Physiol.Pharmacol. 50:740–752.CrossRefGoogle Scholar
  26. 26.
    Koyama, I. and Jasper, H. 1977, Amino acid content of chronic undercut cortex of the cat in relation to electrical afterdischarge: comparison with cobalt epileptogenic lesions, Can.J.Physiol.Pharmacol. 55:523–536.CrossRefGoogle Scholar
  27. 27.
    Lehmann, A., Hagberg, H., Huxtable, R.J., and Sandberg, M. 1987, Reduction of brain taurine: effects on neurotoxic and metabolic actions of kainate, Neurochem.International, 10:265–274.CrossRefGoogle Scholar
  28. 28.
    Lehmann, A., Hagberg, H., Nystrom, B., Sandberg, M., and Hamberger, A. 1985, In vivo regulation of extracellular taurine and other neuroactive amino acids in the rabbit hippocampus, in: “Taurine: Biological Actions and Clinical Perspectives”, Oja, S.S., Ahtee, L., Kontro, P. and Paasonen, M.K. eds., A. R. Liss, New York, pp. 289–311.Google Scholar
  29. 29.
    Lehmann, A., Isacsson, H., and Hamberger, A. 1983, Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus, J.Neurochem. 40:1314–1320.CrossRefGoogle Scholar
  30. 30.
    Lehmann, A., Sandberg, M., and Huxtable, R.J. 1986, In vivo release of neuroactive amines and amino acids from the hippocampus of seizure-resistant and seizure-susceptible rats, Neurochem.International, 8:513–520.CrossRefGoogle Scholar
  31. 31.
    Lowry, O.J., Rosebrough, N.J., Farr, A.L., and Randall, R.J. 1951, Protein measurement with folin phenol reagent, J.Biol.Chem. 193:265–275.Google Scholar
  32. 32.
    Oja, S.S. and Kontro, P. 1983, Free amino acids in epilepsy: possible role of taurine, Acta Neurol.Scand. 67, Suppl.93:5–20.Google Scholar
  33. 33.
    Perry, T.L., Berry, K., Hansen, S., Diamond, S., and Mok, C. 1971, Regional distribution of amino acids in human brain obtained at autopsy, J.Neurochem. 18:513–519.CrossRefGoogle Scholar
  34. 34.
    Perry, T.L. and Hansen, S. 1976, Taurine content of epileptogenic foci in human brain, in: “Taurine”, Huxtable, R. and Barbeau, A. eds., Raven Press, New York, pp. 275–281.Google Scholar
  35. 35.
    Perry, T.L. and Hansen, S. 1981, Amino acid abnormalities in epileptogenic foci, Neurology, 31:872–876.CrossRefGoogle Scholar
  36. 36.
    Perry, T.L., Hansen, S., Kennedy, J., Wada, J., and Thompson, G.B. 1975, Amino acids in human epileptogenic foci, Arch.Neurol. 32:752–754.CrossRefGoogle Scholar
  37. 37.
    Rassin, D.K. 1982, Taurine, cysteine sulfinic acid decarboxylase and glutamic acid in brain, in: “Taurine in Nutrition and Neurology”, Huxtable, R.J. and Pasantes-Morales, H. eds., Plenum Press, New York, pp. 257–268.CrossRefGoogle Scholar
  38. 38.
    Sherwin, A., Robitaille, Y., Quesney, F., Olivier, A., Villemure, J., Leblanc, R., Feindel, W., Andermann, E., Gotman, J., Andermann, F., Ethier, R., and Kish, S. 1988, Excitatory amino acids are elevated in human epileptic cerebral cortex, Neurology, 38:920–923.CrossRefGoogle Scholar
  39. 39.
    Tapia, R. and Gonzalez, R.M. 1978, Glutamine and glutamate as precursors of the releasable pool of GABA in brain cortex slices, Neuroscience Letters, 10:165–169.CrossRefGoogle Scholar
  40. 40.
    Tapia, R., Pasantes, H., Perez De La Mora, M., Ortega, B., and Massieu, G. 1967, Free amino acids and glutamate decarboxylase activity in brain of mice during drug induced convulsions, Biochem. Pharmacol. 16:1211–1227.CrossRefGoogle Scholar
  41. 41.
    Tappaz, M., Almarghini, K., and Do, K. 1994, Cysteine sulfinate decarboxylase in brain: Identification, characterization and immunocytochemical localization in astrocytes, in: “Taurine in Health and Disease”, Huxtable, R.J. and Michalk, D. eds., Plenum Press, New York, pp. 387-402 This volum.Google Scholar
  42. 42.
    Van Gelder, N.M. 1978, Glutamic acid and epilepsy: the action of taurine, in: “Taurine and Neurological Disorders”, Barbeau, A. and Huxtable, R. eds., Raven Press, New York, pp. 387–402.Google Scholar
  43. 43.
    Van Gelder, N.M. 1981, The role of taurine and glutamic acid in the epileptic process: a genetic predisposition, Rev.Pure Appl.Pharmacol.Sci. 2:293–316.Google Scholar
  44. 44.
    Van Gelder, N.M. 1981, Glutamic acid in nervous tissue and changes of the taurine content: its implication in the treatment of epilepsy, in: “Amino Acid Neurotransmitter”, DeFeudis, F.V. and Mandel, P. eds., Raven Press, New York, pp. 115–125.Google Scholar
  45. 45.
    Van Gelder, N.M. 1982, Changed taurine-glutamic acid content and altered nervous tissue cytoarchitecture, in: “Taurine in Nutrition and Neurology”, Huxtable, R.J. and Pasantes-Morales, H. eds., Plenum Press, New York, pp. 239–256.CrossRefGoogle Scholar
  46. 46.
    Van Gelder, N.M. 1983, Metabolic interactions between neurons and astroglia: glutamine synthetase, carbonic anhydrase, and water balance, in: “Basic mechanisms of neuronal hyperexcitability”, Anonymous Alan R. Liss, Inc., New York, pp. 5–29.Google Scholar
  47. 47.
    Van Gelder, N.M. and Courtois, A. 1972, Close correlation between changing content of specific amino acids in epileptogenic cortex of cats, and severity of epilepsy, Brain Res. 43:477–484.CrossRefGoogle Scholar
  48. 48.
    Van Gelder, N.M., Edmonds, H.L., Jr., Hegreberg, G.A., Chatburn, C.C., Clemmons, R.M., and Sylvester, D.M. 1980, Amino acid changes in a genetic strain of epileptic beagle dogs, J.Neurochem. 35:1087–1091.CrossRefGoogle Scholar
  49. 49.
    Van Gelder, N.M., Janjua, N.A., Metrakos, K., MacGibbon, B., and Metrakos, J.D. 1980, Plasma amino acids in 3/sec spikewave epilepsy, Neurochem.Res. 5:659–671.CrossRefGoogle Scholar
  50. 50.
    Van Gelder, N.M., Sherwin, A.L., and Rasmussen, T. 1972, Amino acid content of epileptogenic human brain: focal versus surrounding regions, Brain Res. 40:385–393.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • P.-L. Lleu
    • 1
  • D. Labiner
    • 1
  • M. Weinand
    • 1
  • R. J. Huxtable
    • 1
  1. 1.College of MedicineUniversity of Arizona Health Sciences CenterTucsonUSA

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