The Usefulness of Studies In Vitro for Understanding Cerebral Metabolite Transport In Vivo

  • Abel Lajtha
  • Miriam Banay-Schwartz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 69)


Arguments between proponents of experimentation in vivo and those who favor studying systems in vitro are quite old. The former say that complex living systems cannot be studied in vitro because the changes in these preparations cause observations of artifacts, while the latter say that complex systems have first to be broken into simpler ones before we can hope for meaningful interpretations of our observations. We belong to what we perceive to be the majority, who feel that both approaches are very useful and necessary for studies of nervous system function, and are aware of the need to know the advantages and limitations of both. Similar discussions can still be heard among researchers studying neural barriers: “the blood-brain barrier (and other brain barriers) can be studied only in living animals; perhaps the biggest change in any system in vitro is the absence of the barrier)”, is the statement often heard. Clearly, if we want to study the initial rate of transport from the circulating plasma into brain, studies in vivo are the most suitable; but if we want to study the factors that determine the equilibrium and influence flux, cellular transport processes (requiring observations in vitro) should not be neglected. Hence this chapter.


Olfactory Bulb Brain Research Brain Slice Amino Acid Transport Amino Acid Uptake 
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  1. 1.
    Banay-Schwartz, M., Gergely, A., and Lajtha, A., Independence of amino acid uptake of tissue swelling in incubated slices of brain, Brain Research, 65 (1974) 265–276.CrossRefGoogle Scholar
  2. 2.
    Banay-Schwartz, M., Piro, L., and Lajtha, A., Relationship of ATP levels to amino acid transport in slices of mouse brain, Arch. Biochem.Biophys., 145 (1971) 199–210.CrossRefGoogle Scholar
  3. 3.
    Banay-Schwartz, M., Teller, D.N., Gergely, A., and Lajtha, A., The effects of metabolic inhibitors on amino acid uptake and the levels of ATP, Na+, and K+ in incubated slices of mouse brain. Brain Research, 71 (1974) 117–131.CrossRefGoogle Scholar
  4. 4.
    Banay-Schwartz, M., Teller, D.N., and Lajtha, A.,Energetics of low-affinity amino acid transport into brain slices. In G. Levi, L. Battistin and A. Lajtha (Eds.), Transport Phenomena in the Nervous System,(this volume), Plenum Press, New York, 1976, in press.Google Scholar
  5. 5.
    Banay-Schwartz, M., Teller, D.N., and Lajtha, A.,in preparation.Google Scholar
  6. 6.
    Battistin, L., Grynbaum, A., and Lajtha, A., The uptake of various amino acids by the mouse brain in vivo. Brain Research, 29 (1971) 85–99.CrossRefGoogle Scholar
  7. 7.
    Bauman, A., Bourgoin, S., Benda, P., Glowinski, J., and Hamon, M.,Characteristics of tryptophan accumulation by glial cells. Brain Research, 66 (1974) 253–263.CrossRefGoogle Scholar
  8. 8.
    Bennett, J.P. Jr., Logan, W.J., and Snyder, S.H., Amino acids as central nervous transmitters: the influence of ions, amino acid analogues, and ontogeny on transport systems for L-glutamic and aspartic acids and glycine into central nervous synaptosomes of the rat, J. Neurochem., 21 (1973) 1533–1550.CrossRefGoogle Scholar
  9. 9.
    Bennett, J.P., Mulder, A.H., and Snyder, S.H.,Neurochemical correlates of synaptically active amino acids. Life Sci., 15 (1974) 1045–1056.CrossRefGoogle Scholar
  10. 10.
    Berl, S., Clarke, D., and Schneider, D.(Eds.), Metabolic compartmentation and neurotransmission: relationship of structure and function. Plenum Press, 1976, in press.Google Scholar
  11. 11.
    Berl, S., Nicklas, W.J., and Clarke, D.D.,Compartmentation of glutamic acid metabolism in brain slices, J.Neurochem., 15 (1968) 131–140.CrossRefGoogle Scholar
  12. 12.
    Blasberg, R., and Lajtha, A., Substrate specificity of steady- state amino acid transport in mouse brain slices. Arch.Biochem. Biophys., 112 (1965) 361–377.CrossRefGoogle Scholar
  13. 13.
    Blasberg, R., and Lajtha, A., Heterogeneity of the mediated transport systems of amino acid uptake in brain. Brain Research, 1 (1966) 86–104.CrossRefGoogle Scholar
  14. 14.
    Bourke, R.S., and Tower, D.B., Fluid compartmentation and electrolytes of cat cerebral cortex in vitro. I. Swelling and solute distribution in mature cerebral cortex,.Neurochem., 13 (1966) 1071–1097.CrossRefGoogle Scholar
  15. 15.
    Christensen, H.N., Biological Transport (2nd ed.), W.A.Benjamin, Inc., Reading, Massachusetts, 1975Google Scholar
  16. 16.
    Davis, J.M., and Himwich, W.A., Amino acids and proteins of developing mammalian brain. In W. Himwich (Ed.), Biochemistry of the Developing Brain, Vol.1, Marcel Dekker, New York, 1973, pp.55–110.Google Scholar
  17. 17.
    De Belleroche, J.S., and Bradford, H.F.,Amino acids in synaptic vesicles from mammalian cerebral cortex: a reappraisal, Neurochem., 21 (1973) 441–451.CrossRefGoogle Scholar
  18. 18.
    Dunlop, D.S., van Eiden, W., and Lajtha, A., Measurements of rates of protein synthesis in rat brain slices, J. Neurochem., 22 (1974) 821–830.CrossRefGoogle Scholar
  19. 19.
    Dunlop, D.S., van Eiden, W., and Lajtha, A., A method for measuring brain protein synthesis rates in young and adult rats, J. Neurochem. 24 (1975) 337–344.CrossRefGoogle Scholar
  20. 20.
    Dunlop, D.S., van Eiden, W., and Lajtha, A., Optimal conditions for protein synthesis in incubated slices of rat brain. Brain Research,99 (1975) 303–318.CrossRefGoogle Scholar
  21. 21.
    Felig, P., Wahren, J., and Ahlborg, G., Uptake of individual amino acids by the human brain, Proc.Soc.Exp.Biol.Med., 142 (1973) 230–231.CrossRefGoogle Scholar
  22. 22.
    Felig, P., Amino acid metabolism in man, Ann.Rev.Biochem., 44 (1975) 933–955.CrossRefGoogle Scholar
  23. 23.
    Garfinkel, D., London, J.W., Dzubow, L., and Nicklas, W.J., Computer simulation of the metabolism of guinea pig brain slices, and how they differ from the intact brain. Brain Research, 92 (1975) 207–218.CrossRefGoogle Scholar
  24. 24.
    Gilbert, B.E., and Johnson, T.C., Protein turnover during maturation in mouse brain tissue, J.Cell Biol., 53 (1972) 143–147.CrossRefGoogle Scholar
  25. 25.
    Hamberger, A., Amino acid uptake in neuronal and glial cell fractions from rabbit cerebral cortex. Brain Research, 31 (1971) 169–178.CrossRefGoogle Scholar
  26. 26.
    Henn, F.A., Goldstein, M.N., and Hamberger, A.,Uptake of the neurotransmitter candidate glutamate by glia. Science, 249 (1974) 663–664.Google Scholar
  27. 27.
    Himwich, W.A., and Agrawal, H.C., Amino acids, In A. Lajtha (Ed.), Handbook of Neurochemistry, Vol.1, Plenum Press, New York, 1969, pp.33–52.Google Scholar
  28. 28.
    Iversen, L.L., and Bloom, F.E., Studies of the uptake of H- GABA and (3H) glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography. Brain Research, 41 (1972) 131–143.CrossRefGoogle Scholar
  29. 29.
    Kandera, J., Levi, G., and Lajtha, A., Control of cerebral metabolite levels - II. Amino acid uptake and levels in various areas of the rat brain, Arch.Biochem.Biophys., 126 (1968) 249–260.CrossRefGoogle Scholar
  30. 30.
    Lajtha, A., Transport as control mechanism of cerebral metabolite levels. In A. Lajtha and D.H. Ford (Eds.), Progress in Brain Research, Vol.29, Elsevier, Amsterdam, 1968, pp.201–218.Google Scholar
  31. 31.
    Lajtha, A., Amino acid transport in the brain in vivo and in vitro. In Ciba Foundation S3nnposium, Vol.22, Elsevier, Amsterdam, 1974, pp.25–49.Google Scholar
  32. 32.
    Lajtha, A., Transport and incorporation of amino acids in relation to measurement of axonal flow, In W.M. Cowan and M. Cuenod (Eds.), The Use of Axonal Transport for Studies of Neuronal Connectivity, Elsevier, Amsterdam, 1975, pp.25–45.Google Scholar
  33. 33.
    Lajtha, A., and Dunlop, D., Alterations of protein metabolism during development of the brain. In A. Vernadakis and N. Weiner (Eds.), Drugs and the Developing Brain,Plenum Press, New York, 1974, pp.215–229.CrossRefGoogle Scholar
  34. 34.
    Lajtha, A., Latzkovits, L., and Toth, J., Comparison of turnover rates of proteins of the brain, liver and kidney in mouse in vivo following long term labeling, Biochim.Biophys.Acta, 1976, in press.Google Scholar
  35. 35.
    Lajtha, A., and Sershen, H., Substrate specificity of uptake of diamines in mouse brain slices, Arch.Biochem.Biophys., 165 (1974) 539–547.CrossRefGoogle Scholar
  36. 36.
    Lajtha, A., and Sershen, H., Inhibition of amino acid uptake by the absence of Na+ in slices of brain, J.Neurochem., 24 (1975) 667–672.CrossRefGoogle Scholar
  37. 37.
    Lajtha, A., and Sershen, H., Changes in amino acid influx with Na+ flow in incubated slices of mouse brain. Brain Research, 84 (1975) 429–441.CrossRefGoogle Scholar
  38. 38.
    Lajtha, A., and Toth, J., Instability of cerebral proteins, Biochem.Biophys.Res.Comm., 23 (1966) 294–298.CrossRefGoogle Scholar
  39. 39.
    Lajtha, A., and Toth, J., Perinatal changes in the free amino acid pool of the brain in mice. Brain Research,55 (1973) 238–241.CrossRefGoogle Scholar
  40. 40.
    Levi, G., Development of amino acid transport systems in incubated tissue. In W. Himwich (Ed.), Biochemistry of the Developing Brain, Vol.1, Marcel Dekker, 1973, pp.187–218.Google Scholar
  41. 41.
    Levi, G., Kandera, J., and Lajtha, A., Control of cerebral metabolite levels.I. Amino acid uptake and levels in various species. Arch.Biochem.Biophys., 119 (1967) 303–311.CrossRefGoogle Scholar
  42. 42.
    Levi, G., and Raiteri, M., Detectability of high and low affinity uptake systems for GABA and glutamate in rat brain slices and synaptosomes. Life Sci., 12 (1973) 81–88.CrossRefGoogle Scholar
  43. 43.
    Levi, G., and Raiteri, M., GABA and glutamate uptake by subcellular fractions enriched in synaptosomes: critical evaluation of some methodological aspects. Brain Research, 57 (1973) 165–186.CrossRefGoogle Scholar
  44. 44.
    Levi, G., and Raiteri, M.,Exchange of neurotransmitter amino acid at nerve endings can simulate high affinity uptake. Nature, 250 (1974) 735–737.ADSCrossRefGoogle Scholar
  45. 45.
    Ludt, H., and Dittman, J., Advantages of defined tissue slices against minced samples in biochemical in vitro investigations of brain cortex. Acta Biol.Med.Germ., 34 (1975) 189–195.PubMedGoogle Scholar
  46. 46.
    Mangan, J.L. and Whittaker, V.P., The distribution of free amino acids in subcellular fractions of guinea-pig brain. Biochemical Journal, 98 (1966) 128–137.CrossRefGoogle Scholar
  47. 47.
    Margolis, R., and Lajtha, A., Ion dependence of amino acid uptake in brain slices, Biochim.Biophys.Acta, 163 (1968) 374–385.CrossRefGoogle Scholar
  48. 48.
    Marks, N., Stern, F., and Lajtha, A., Changes in proteolytic enzymes and proteins during maturation of the brain. Brain Research, 86 (1975) 307–322.CrossRefGoogle Scholar
  49. 49.
    Navon, S., and Lajtha, A.,The uptake of amino acids by particulate fractions from brain, Biochim.Biophys.Acta,173 (1969) 518–531.CrossRefGoogle Scholar
  50. 50.
    Neidle, A., Kandera, J., and Lajtha, A., The uptake of amino acids by the intact olfactory bulb of the mouse: A comparison with tissue slice preparations, J.Neurochem.20 (1973) 1181–1193.CrossRefGoogle Scholar
  51. 51.
    Neidle, A., Kandera, J., and Lajtha, A., Compartmentation and exchangeability of brain amino acids: Evidence from studies of transport into tissue slices, Arch.Biochem.Biophys., 169 (1975) 397–405.CrossRefGoogle Scholar
  52. 52.
    Oja, S.S., Incorporation of phenylalanine, tyrosine and tryptophan into protein of homogenates from developing rat brain: kinetics of incorporation and reciprocal inhibition, J.Neuro- chem., 19 (1972) 2057–2069.Google Scholar
  53. 53.
    Oja, S.S., and Vahvelainen, M.L., Transport of amino acids in brain slices. In N. Marks and R. Rodnight (Eds.), Research Methods in Neurochemistry, Vol.3, Plenum Press, New York, 1975, pp.67–137.CrossRefGoogle Scholar
  54. 54.
    Okamoto, K., and Quastel, J.H., Uptake and release of glutamate in cerebral-cortex slices from the rat, Biochem.J., 128 (1972) 1117–1124.CrossRefGoogle Scholar
  55. 55.
    Oldendorf, W.H., Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection, Amer.J.Physiol., 221 (1972) 1629–1639.CrossRefGoogle Scholar
  56. 56.
    Oldendorf, W.H., and Szabo, J., Amino acid assignment to one of three blood brain barrier amino acid carriers, Amer.J.Physiol., 1975, in pressGoogle Scholar
  57. 57.
    Piccoli, F., Grynbaum, A., and Lajtha, A., Developmental changes in Na+, K+ and ATP and in the levels and transport of amino acids in incubated slices of rat brain, J.Neurochem., 18 (1971) 1135–1148.CrossRefGoogle Scholar
  58. 58.
    Pull, I., Jones, D.A., and Mcllwain, H., Superfused cerebral tissues in hypoxia: neurotransmitter and amino acid retention; labile constituents and response to excitation, J.Neurobiol., 3 (1972) 311–323.CrossRefGoogle Scholar
  59. 59.
    Roberts, S., Effects of amino acid imbalance on amino acid utilization, protein synthesis and polyribosome function in cerebral cortex. In Aromatic Amino Acids in the Brain, CIBA Foundation Symposium 22, American Elsevier, New York, 1974, pp.299–324.Google Scholar
  60. 60.
    Rose, S.P.R., and Sinha, A.K., Some properties of isolated neuronal cell fractions, J.Neurochem., 16 (1969) 1319–1329.CrossRefGoogle Scholar
  61. 61.
    Sershen, H., and Lajtha, A.,The distribution of amino acids, Na+, and K+ from surface to centre in incubated slices of mouse brain, J.Neurochem., 22 (1974) 977–985.CrossRefGoogle Scholar
  62. 62.
    Sershen, H., and Lajtha, A., in preparation.Google Scholar
  63. 63.
    Seta, K., Sansur, M., and Lajtha, A., The rate of incorporation of amino acids into brain proteins during infusion in the rat, Biochim.Biophys.Acta, 294 (1973) 472–480.CrossRefGoogle Scholar
  64. 64.
    Snyder, S.H., Young, A.B., Bennett, J.P, and Mulder, A.H., Synaptic biochemistry of amino acids, Fed.Proc., 32 (1973) 2039–2047.PubMedGoogle Scholar
  65. 65.
    Teller, D.N., Banay-Schwartz, M., De Guzman, T., and Lajtha, A., Energetics of amino acid transport into brain slices. Effects of glucose depletion and substitution of Krebs cycle intermediates, Brain Research,1976, in press.Google Scholar
  66. 66.
    Wade, L.A., and Katzman, R., Transport of L-DOPA and related amino acids across cerebral capillaries: evidence for the presence of the L transport system. Abstracts 5th Meeting Internatl.Soc.Neurochem., Barcelona,1975, p.462.Google Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Abel Lajtha
    • 1
  • Miriam Banay-Schwartz
    • 1
  1. 1.New York State Research Institute for Neurochemistry and Drug AddictionWard’s Island, New YorkUSA

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