Abstract
Thiamine phosphate esters (thiamine monophosphate-TMP; thiamine diphosphate-TDP and thiamine triphosphate-TTP) were measured as their thiochrome derivatives by High Performance Liquid Chromatography in the brains of pyrithiamine-treated rats at various stages during the development of thiamine deficiency encephalopathy. Severe encephalopathy was accompanied by significant reductions of all three thiamine phosphate esters in brain. Neurological symptoms of thiamine deficiency appeared when brain levels of TMP and TDP fell below 15% of normal values. Activities of the TDP-dependent enzyme α-ketoglutarate dehydrogenase were more severely reduced in thalamus compared to cerebral cortex, a less vulnerable brain structure. On the other hand, reductions of TTP, the non-cofactor form of thiamine, occurred to a greater extent in cerebral cortex than thalamus. Early reductions of TDP-dependent enzymes and the ensuing metabolic pertubations such as lactic acidosis impaired brain energy metabolism, and NMDA-receptor mediated excitotoxicity offer rational explanations for the selective vulnerability of brain structures such as thalamus to the deleterious effects of thiamine deficiency.
Similar content being viewed by others
References
Butterworth R. F. 1989. Effects of thiamine deficiency on brain metabolism: implications for the pathogenesis of the Wernicke-Korsakoff Syndrome. Alcohol & Alcoholism 24:271–279.
Butterworth, R. F., Gaudreau, C., Vincelette, J., Bourgault, A. M., Lamothe F., and Nutini, A.-M. 1991. Thiamine deficiency and Wernicke's Encephalopathy in AIDS. Metab. Brain Dis. 6:207–212.
Victor, M., Adams, R. D., and Collins, G. H. 1989. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. 2nd Ed. F.A. Davis Co. Philadelphia.
Bettendorff, L., Peeters, M., Wins, P. and Schoffeniels, E. 1993. Metabolism of thiamine triphosphate in rat brain: correlation with chloride permeability. J. Neurochem. 60:423–434.
Peters, R. A. 1936. The biochemical lesion in vitamin B1 deficiency. Application of modern biochemical analysis in its diagnosis. The Lancet (i), 1161–1164.
Gibson, G. E., Ksiezak-Reding, H., Sheu, K. F. R., Mykytyn, V. and Blass, J. P. 1984. Correlation of enzymatic, metabolic and behavioral deficits in thiamin deficiency and its reversal. Neurochem. Res. 9:803–814.
Butterworth, R. F., Giguère, J. F., and Bernard, A. M. 1986. Activities of thiamine-dependent enzymes in two experimental models of thiamine-deficiency encephalopathy. 2. α-ketoglutarate dehydrogenase. Neurochem. Res. 11:567–577.
Butterworth, R. F., and Héroux, M. 1989. Effect of pyrithiamine treatment and subsequent thiamine rehabilitation on regional cerebral amino acids and thiamine-dependent enzymes. J. Neurochem. 52:1079–1084.
Troncoso, J. C., Johnston, M. V., Hess, K. M., Griffin, J. W., Price, D. L. 1981. Model of Wernicke's Encephalopathy. Arch Neurol. 38:350–354.
Aikawa, H., Watanabe, I. S., Furuse T., Iwasaki, Y., Satoyoshi, E., Sumi, T., and Moroji, T. 1984. Low energy levels in thiamine-deficient encephalopathy. J. Neuropathol. and Exp. Neurol. 43: 276–287.
Hakim, A. M. 1984. The induction and reversibility of cerebral acidosis in thiamine deficiency. Ann. Neurol. 16:673–679.
Jolicoeur, F. B., Rondeau, D. B., Hamel, E., Butterworth, R. F., and Barbeau, A. 1979. Measurement of ataxia and related neurological signs in the laboratory rat. Can. J. Neurol. Sci. 6:209–216.
Glowinski, J., and Iversen, L. L. 1966. Regional studies of catecholamines in the rat brain. J. Neurochem. 13:655–669.
Bettendorff, L., Grandfils, C., De Rycker, C., Schoffeniels E. 1986. Determination of thiamine and its phosphate esters in human blood serum at femtomole levels. J. Chromatogr. 382:297–302.
Sen, I., and Cooper, J. R. 1976. The turnover of thiamine and its phosphate esters in rat organs. Neurochem. Res. 1:65–71.
Giguère, J. F. and Butterworth, R. F. 1987. Activities of thiamine-dependent enzymes in two experimental models of thiamine deficiency encephalopathy: 3. Transketolase. Neurochem. Res. 12: 305–310.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.
Rindi, G., and deGiusseppe, L. 1961. A new chromatographic method for the determination of thiamine and its mono-, di- and triphosphates in animal tissues. Biochem. J. 78:602–606.
Ishii, K., Sarai, K., Sanemori, H. and Kawasaki, T. 1979. Analysis of thiamine and its phosphate esters by high-performance liquid chromatography. Anal. Biochem. 97:191–195.
Rindi, G. and Perri, V. 1961. Uptake of pyrithiamine by tissue of rats. Biochem. J. 80:214–216.
Rindi, G., Patrini, Comincioli, V., and Reggiani, C. 1980. Thiamine content and turnover rates of some rat nervous regions, using labeled thiamine as a tracer. Brain Res. 181:369–380.
Rindi, G., Comincioli, V., Reggiani, C., and Patrini, C. 1984. Nervous tissue thiamine metabolism in vivo. II. Thiamine and its phosphoesters dynamics in different brain regions and sciatic nerve of the rat. Brain Res. 293:329–342.
Langlais, P. J., and Mair R. G. 1990. Protective effects of the glutamate antagonist MK801 on pyrithiamine-induced lesions and amino acid changes in rat brain. J. Neurosci. 10:1664–1674.
Héroux, M., and Butterworth, R. F. 1988. Reversible alterations of cerebral γ-aminobutyric acid in pyrithiamine-treated rats: implications for the pathogenesis of Wernicke's Encephalopathy. J. Neurochem. 51:1221–1226.
Butterworth, R. F. 1993. Pathophysiologic mechanisms responsible for the reversible (thiamine responsive) and irreversible (thiamine non-responsive) neurological signs of Wernicke's Encephalopathy. Drug and Alcohol Review 12:317–324, 1993.
Gaitonde M. K., Fayein, N. A., and Johnson, A. L. 1975. Decreased metabolism in vivo of glucose into amino acids of the brain of thiamine treated rats after treatment with pyrithiamine. J. Neurochem. 24:1215–1223.
Holowach, J., Kauffman, F., Ikossi, M. G., Thomas C. and McDougal D.B. 1968. The effects of a thiamine antagonist, pyrithiamine, on levels of selective metabolic intermediates and on activities of thiamine-dependent enzymes in brain and liver. J. Neurochem. 15:621–631.
Kauppinen, R. A., McMahon, H. T., and Nichols, D. G. 1988. Ca2+-dependent and Ca2+-independent glutamate release, energy status and cytosolic free Ca2+ concentration in isolated nerve terminals following metabolic inhibition: possible relevance to hypoglycaemia and anoxia. Neuroscience 27:175–182.
Hazell, A. S., Butterworth, R. F., and Hakim, A. M. 1993. Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency. J. Neurochem. 61:1155–1158.
Langlais, P. J., and Zhang, S. X. 1993. Extracellular glutamate is increased in thalamus during thiamine deficiency included lesions and is blocked by MK801. J. Neurochem. 61:2175–2182, 1993.
Leong, D. K., Oliva, L. and Butterworth. 1994. Reductions of neuronal loss in thalamus of thiamine deficient rats by MK801: correlation with3H-PK11195 binding sites.Soc. Neurosci. Abs. 20:122.16.
Héroux, M., and Butterworth, R. F. 1992. Animal models of the Wernicke-Korsakoff Syndrome, inNeuromethods, vol. 22: Animal Models of Neurological Disease. II. (A. A. Boulton, G. B. Baker and R. F. Butterworth, eds). Humana Press Inc., New Jersey, 95–131.
Leong, D. K., Le O., Oliva, L., and Butterworth, R. F. 1994. Increased densities of binding sites for the “peripheral-type” benzodiazepine receptor ligand3H-PK11195 in vulnerable regions of the rat brain in thiamine deficiency encephalopathy. J. Cerebr. Blood Flow Metab. 14:100–105.
Butterworth, R. F., Kril, J. J. and Harper, C. G. 1993. Thiamine-dependendent enzyme changes in the brains of alcoholics: relationship to the Wernicke-Korsakoff Syndrome. Alcoholism: Clin. and Exp. Res. 17:1084–1088.
Mair, R. G., Knoth, R. L., Rabchenuk, S. A., and Langlais, P. J. 1991. Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency. Behav. Neurosci. 105:360–374.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Héroux, M., Butterworth, R.F. Regional alterations of thiamine phosphate esters and of thiamine diphosphate-dependent enzymes in relation to function in experimental Wernicke's encephalopathy. Neurochem Res 20, 87–93 (1995). https://doi.org/10.1007/BF00995157
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00995157