Brain Damage and Oral Intake of Certain Amino Acids

  • John W. Olney
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 69)


The primary focus in this chapter will be on glutamate (GLU) and certain of its structural analogues which I shall refer to as the excitotoxic amino acids because of specific neuroexcitatory and neurotoxic properties which characterize these acidic amino acids as a group. Brief attention will be given separately to L-cysteine (CYS) which, when given orally to experimental animals, induces a different neurotoxic syndrome from that caused by oral intake of excitotoxic amino acids. Most of the evidence I shall review pertains to excitotoxic amino acids as a group but derives from studies on GLU, the prototypic and most studied member of the group.


Brain Damage Arcuate Nucleus Lower Effective Dose Monosodium Glutamate Venezuelan Equine Encephalitis Virus 
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  1. 1.
    Balcar, V.J. and Johnston, G.A.R., The structural specificity of high affinity uptake of L-glutamate and L-aspartate by rat brain slices. J. Neurochem. 19 (1972) 2657–2166.CrossRefPubMedGoogle Scholar
  2. 2.
    Bessman, S., Magnes, J., Schwerin, P. and Waelsch, H., Absorption of glutamate and glutamine. Biol. Chem. 175 (1948) 817–823.Google Scholar
  3. 3.
    Bürde, R., Schainker, B., Kayes, J., Monosodium glutamate acute effect of oral and subcutaneous administration on the arcuate nucleus. Nature 233 (1974) 58–60.ADSCrossRefGoogle Scholar
  4. 4.
    Curtis, D. and Watkins, J., Acidic amino acids with strong excitatory action on mammalian neurons. Physiol. 166 (1963) 1–8.CrossRefGoogle Scholar
  5. 5.
    Dent, C. and Schilling, J., Protein absorption: the amino acid pattern in the portal blood. Biochem. J. 44 (1949) 318–333.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Feigin, R., Jaeger, R., McKinney, R., Attenuated Venezuelan equine encephalitis virus II: amino acid studies following immunization. J. Trop. Med. Hyg. 16 (1967) 769–781.CrossRefGoogle Scholar
  7. 7.
    Gutman, A.B., Yu, T.F., Hyperglutamatemia in primary gout. M. J. 54 (1973) 713–717.Google Scholar
  8. 8.
    Himwich, W.A. and Peterson, I.M., Ingested glutamate and plasma levels of glutamic acido J. Appl. Physiol. 7 (1954) 196–201.CrossRefPubMedGoogle Scholar
  9. 9.
    Lemkey-Johnston and Reynolds, W.A., Nature and extent of brain lesions in mice related to ingestion of monosodium glutamate. J. Neuropath. & Exp. Neurol. 33 (1974) 74–97.CrossRefGoogle Scholar
  10. 10.
    McLaughlan, J., Noel, F., Botting, H. and Knipfel, J., Blood and brain levels of glutamic acid in young rats given monosodium glutamate. Nutr. Rep. Int. 1:2 (1970) 131–138.Google Scholar
  11. 11.
    Misra, C.H. and Olney, J.W., Cysteine oxidase in brain. Brain Res. J 97 (1975) 117–126.CrossRefGoogle Scholar
  12. 12.
    Olney, J.W., Brain lesions, obesity and other disturbances in mice treated with glutamate. Science 164 (1969) 719–720.ADSCrossRefPubMedGoogle Scholar
  13. 13.
    Olney, J.W., Glutamate-induced neuronal necrosis in the infant mouse hypothalamuso Neuropath. & Exp. Neurol., 30 (1971) 75–90.CrossRefGoogle Scholar
  14. 14.
    Olney, J.W., Occult mechanisms of brain damage. In A. Vernadakis and N. Weiner (Eds.), Proceedings of Symposium on Drugs and Developing Brain. Plenum Press, New York, 1974, pp. 489–501.CrossRefGoogle Scholar
  15. 15.
    Olney, J.W., Neurotoxic effects of glutamate and related amino acids. In W.L. Nyhan (Ed.), Heritable Disorders of Amino Acid Metabolism, John Wiley & Sons, Inc., N.Y., 1974, pp. 501–512.Google Scholar
  16. 16.
    Olney, J.W. and Ho, O.L., Brain damage in infant mice from oral intake of glutamate, aspartate or cysteine. Nature 227 (1970) 609.ADSCrossRefGoogle Scholar
  17. 17.
    Olney, J.W., Ho, O.L. and Rhee, V., Cytotoxic effects of acidic and sulphur-containing amino acids on the infant mouse central nervous system. Exp. Br. Res., 14 (1972) 61–76.Google Scholar
  18. 18.
    Olney, J.W., Ho, O.L., Rhee, V. and de Gubareff, T., Neurotoxic effects of glutamate. New Eng. J. Med. 289 (1973) 1374–1375.CrossRefPubMedGoogle Scholar
  19. 19.
    Olney, J.W., Ho, O.L., Rhee, V., Schainker, B., Cysteine brain damage in infant and fetal rodents. Brain Res. 45 (1972) 309–313.CrossRefPubMedGoogle Scholar
  20. 20.
    Olney, J.W., Rhee, V. and Ho, O.L., Kainic acid: A powerful neurotoxic analogue of glutamate. Brain Res. 77 (1974) 507–512.CrossRefPubMedGoogle Scholar
  21. 21.
    Olney, J.W, Sharpe, L.G. and de Gubareff, T., Excitotoxic amino acids (Abstr.) Soc. Neurosciences 1975.Google Scholar
  22. 22.
    Olney, J.W., Sharpe, L. and Feigin, R., Glutamate induced brain damage in primates. Neuropath. Expo Neurol. 31 (1972) 464–488CrossRefGoogle Scholar
  23. 23.
    Perez, V.J. and Olney, J.W., Accumulation of glutamic acid in the arcuate nucleus following subcutaneous administration of the amino acid. J. Neurochem. 19 (1972) 1777–1781.CrossRefPubMedGoogle Scholar
  24. 24.
    Pollin, W., Cardon, P. and Kety, S., Schizophrenic patients fed amino acid loads with Iproniazid. Science 175 (1961) 1365–1366.Google Scholar
  25. 25.
    Spaide, J., Davis, J. and Himwich, J., Plasma amino acids in schizophrenic patients fed methionine or cysteine loads with a monoamine oxidase inhibitor. Am. J. Clin. Nutr. 24 (1971) 1053–1059.CrossRefPubMedGoogle Scholar
  26. 26.
    Stegink, L., Filer, L., Baker, G., Glutamate metabolism in the neonatal pig. J. Nutr. 103 (1973) 1138–1145.CrossRefPubMedGoogle Scholar
  27. 27.
    Stegink, L., Filer, L. and Baker, G. Glutamate effect on plasma and breast milk amino acid levels in lactating women. Proc. Soc. Exp. Biol. Med. 149 (1972) 838–841.Google Scholar
  28. 28.
    Stegink, L., Pitkin, R., Reynolds, W., Filer, L., Boaz, D., Brummel, M., Placental transfer of glutamate and its metabolites in the primate. Am. J. Obstet. & Gyn. 122 (1975) 70–78.CrossRefGoogle Scholar
  29. 29.
    Van Harreveld, A. and Fifkova, E., Light and electronmicroscopic changes in central nervous tissue after electrophoretic injection of glutamate. Exp. Molec. Pathol. 15 (1971) 61–81.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • John W. Olney
    • 1
  1. 1.Department of PsychiatryWashington University School of MedicineSt. LouisUSA

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