Skip to main content
Log in

Cycloleucine uptake in the brainstem of thiamine-deficient rats

  • Original Investigations
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Immature female rats were subjected to acute dietary deficiency of thiamine. An autoradiographic method was used in the semi-quantitative determination of concentration of 1-aminocyclopentane-1-carboxylic acid-carboxylic-14C (cycloleucine) in brainstem regions after intravenous administration of tracer quantities. The time course of tissue concentrations was followed and compared with that of normal and isocaloric control animals. Our data indicate that thiamine deficiency of sufficient magnitude to induce brainstem lesions has an effect on the transport of cycloleucine. The initial 2 min values in the nuclear areas are appreciably reduced whereas the 6 min values are significantly elevated as compared with controls; no change was demonstrated in the white matter of the inferior cerebellar peduncle. The effect on transport appears to be more on the mechanism of efflux than of influx in terms of blood brain barrier function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Banay-Schwartz, M., Piro, L., Lajtha, A.: A relationship of ATP levels to amino acid transport in slices of mouse brain. Arch. Biochem. Biophys.145, 199–210 (1971)

    Google Scholar 

  • Banay-Schwartz, M., Teller, D. N., Gergely, A., 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 Res.71, 117–131 (1974)

    Google Scholar 

  • Battistin, L., Lajtha, A.: Regional distribution and movement of amino acids in the brain. J. neurol. Sci.10, 313–322 (1970)

    Google Scholar 

  • Baxter, C. F.: Intrinsic amino acid levels and the blood-brain barrier. In: Brain Barrier Systems (eds. A. Lajtha and D. H. Ford), pp. 429–444 New York: Elsevier 1968

    Google Scholar 

  • Blasberg, R., Lajtha, A.: Heterogeneity of the mediated transport system of amino acid uptake in brain. Brain Res.1, 86–104 (1966)

    Google Scholar 

  • Chirigos, M. A., Greengard, P., Udenfriend, S.: Uptake of tyrosine by rat brain in vivo. J. biol. Chem.235, 2075–2079 (1960)

    Google Scholar 

  • Christensen, H. N., Jones, J. C.: Amino acid transport models. Renal resportion and resistance to metabolic attack. J. biol. Chem.237, 1023–1206 (1962)

    Google Scholar 

  • Cohen, S. R., Lajtha, A.: Amino acid transport. In: Handbook of Neurochemistry (ed. A. Lajtha), pp. 543–572. New York: Plenum Press 1972

    Google Scholar 

  • Gaitonde, M. K., Nixey, R. W. K., Sharman, I. M.: The effect of deficiency of thiamine on the metabolism of [U-14C] glucose and [U-14] ribose and levels of amino acids in rat brain. J. Neurochem.22, 53–61 (1974)

    Google Scholar 

  • Gerschenfeld, H. M., Wald, F., Zadunaisky, J. A., de Robertis, E.: Function of astroglia in the water-ion metabolism of the central nervous system. Neurology (Minneap.)9, 412–425 (1959)

    Google Scholar 

  • Gregory, F. J., Flint, S. F., Ruelius, H. W., Warren, G. H.: Reversal of antileukemic action and toxicity of 1-amino-cyclopentanecarboxylic acid in mice by valine. Cancer Res.29, 728–729 (1969)

    Google Scholar 

  • Gubler, C. J., Adams, B. L., Hammond, B., Yuan, E. C., Guo, S. M., Bennion, M.: Effect of thiamine deprivation and thiamine antagonists on the level of γ-aminobutyric acid and on 2-oxoglutarate metabolism in rat brain. J. Neurochem.22, 831–836 (1974)

    Google Scholar 

  • Haas, R. A., Robertson, D. M., Meyers, N.: Microscopic densitometric system for point measurements of autoradiograms. Stain Technol.50, 137–141 (1975)

    Google Scholar 

  • Johnston, G. A. R.: The intraspinal distribution of some depressant amino acids. J. Neurochem.15, 1013–1017 (1968)

    Google Scholar 

  • Kandera, J., Levi, G., Lajtha, A.: Control of cerebral metabolite levels: II. Amino acid uptake and levels in various areas of the rat brain. Arch. Biochem. Biophys.126, 249–260 (1968)

    Google Scholar 

  • Klatzo, I.: Neuropathological aspects of brain edema. J. Neuropath. exp. Neurol.26, 1–14 (1967)

    Google Scholar 

  • Lajtha, A.: Transport as control mechanism of cerebral metabolite levels. In: Progress in Brain Research, Vol. 28, Brain Barrier System (eds. A. Lajtha and D. H. Ford), pp. 201–216. New York: Elsevier Publishing Co. 1962

    Google Scholar 

  • Lajtha, A., Mela, L.: The brain-barrier system. I. The exchange of free amino acids between plasma and brain. J. Neurochem.7, 210–217 (1961)

    Google Scholar 

  • Lajtha, A., Toth, J.: The brain-barrier system. V. Stereospecificity of amino acid uptake, exchange and efflux. J. Neurochem.10, 909–920 (1963)

    Google Scholar 

  • Lajtha, A., Toth, J.: The effects of drugs on uptake and exit of cerebral amino acids. Biochem. Pharmacol.14, 729–738 (1965)

    Google Scholar 

  • Ling, K.: Some aspects of the active transport of amino acids. Angew. Chem.9, 345–356 (1970)

    Google Scholar 

  • Manz, H. J., Robetson, D. M.: Vascular permeability to horseradish peroxidase in brainstem lesions of thiamine-deficient rats. Amer. J. Path.66, 565–576 (1972)

    Google Scholar 

  • Meyers, N., Haas, R. A., Robertson, D. M., Manz, H. J.: A soluble-compund, radioautography technique. Canad. J. med. Tech.37, 158 (1975)

    Google Scholar 

  • Murray, J. E.: Carrier-mediated transfer of amino acids from blood to brain. An in vivo study in the rat. Neurology (Minneap.)23, 940–944 (1973)

    Google Scholar 

  • Oldendorf, W. H.: Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard. Brain Res.24, 372–376 (1973)

    Google Scholar 

  • Oldendorf, W. H.: Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Amer. J. Physiol.221, 1629–1639 (1971)

    Google Scholar 

  • Orlowski, M., Sessa, G., Green, J. P.: Glutamyl transpeptidase in brain capillaries: Possible site of a blood-brain barrier for amino acid. Science184, 66–68 (1974)

    Google Scholar 

  • Richter, J. J., Wainer, A.: Evidence for separate systems for the transport of neutral and basic amino acids across the blood-brain barrier. J. Neurochem.18, 613–620 (1971)

    Google Scholar 

  • Robertson, D. M., Manz, H. J.: Effect of thiamine deficiency on the competence of the blood-brain barrier to albumin labelled with fluorescent dyes. Amer. J. Path.63, 393–402 (1971)

    Google Scholar 

  • Robertson, D. M., Manz, H. J., Haas, R. A., Meyers, N.: Glucose uptake in the brainstem of thiamine-deficient rats. Amer. J. Path.79, 107–118 (1975)

    Google Scholar 

  • Robertson, D. M., Wasan, S. M., Skinner, D. B.: Ultrastructural features of early brainstem lesions of thiamine-deficient rats. Amer. J. Path.52, 1081–1097 (1968)

    Google Scholar 

  • Snedecor, G., Cochran, W.: Statistical methods, pp. 114, 141 Ames, Iowa: Iowa State University Press 1967

    Google Scholar 

  • Warnock, L. G., Burkhalter, V. J.: Evidence of malfunctioning blood-brain barrier in experimental thiamine deficiency in rats. J. Nutr.94, 256–260 (1968)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by Grant MT 1817 from the Medical Research Council of Canada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manz, H.J., Robertson, D.M., Haas, R.A. et al. Cycloleucine uptake in the brainstem of thiamine-deficient rats. Acta Neuropathol 36, 47–56 (1976). https://doi.org/10.1007/BF00685147

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00685147

Key words

Navigation