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The effect of thiamine deficiency on the structure and physiology of the rat forebrain

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Abstract

Dietary thiamine deficiency, enhanced by pyrithiamine administration in adult rats, produces overt lesions in the brain that are especially prominent in the thalamus. The present study was undertaken to determine whether the thalamic lesions could be correlated with alterations in the physiological properties of neurons in the thalamus and somatosensory cortex. The regimen for experimentally inducing thiamine deficiency produced large lesions in the thalamus of every case; the lesions included most, if not all, of the neurons in the intralaminar thalamic nuclei. The extent of the lesion in the intralaminar thalamus was highly correlated with the loss of bilaterally synchronous spontaneous activity in the cerebral cortex. This correlation was seen in animals analyzed as early as 1–18 hr after the appearance of opisthotonus, the crisis state of thiamine deficiency, and as late as 2–9 weeks of recovery following thiamine replacement therapy. The loss of bilateral synchronous bursting neuronal activity following intralaminar thalamic lesions is consistent with the proposed role of the intralaminar thalamus as a pacemaker for rhythmic cortical activity (Armstrong-Jameset al.,Exp. Brain Res., 1985; Fox and Armstrong-James,Exp. Brain Res. 63: 505–518, 1986). The location and size of the central lesions within the thalamus suggest that the observed neuronal loss could result from a nonhemorrhagic infarction in the ventromedial branches of the superior cerebellar arteries. Experimental thiamine deficiency also produced alterations in the receptive field properties of the somatosensory cortex neurons in all animals examined. Changes in cortical receptive field properties were correlated with the destruction of sensory relay neurons in the thalamic ventrobasal complex. The loss of the central lateral thalamic input to the cortex and the loss of somatosensory relay neurons in the ventrobasal thalamus in experimental thiamine deficiency produce alterations in cortical function which may contribute to deficits in memory and cognition analogous to those which characterize Korsakoff's psychosis in humans.

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References

  • 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. Neuropath. Exp. Neurol. 43: 276–287.

    Google Scholar 

  • Akert, K., Koella, W. P., and Hess, R., Jr. (1952). Sleep produced by electrical stimulation of the thalamus.Am. J. Physiol. 168: 260–267.

    Google Scholar 

  • Armstrong-James, M., and Fox, K. (1983). Effects of ionotophoresed noradrenaline on the spontaneous activity of neurons in rat primary somatomsensory cortex.J. Physiol. 335: 427–447.

    Google Scholar 

  • Armstrong-James, M., and Fox, K. (1984). Similarities in unitary cortical activity between Slow wave sleep and light urethane anesthesia in the rat.J. Physiol. 340: 55P.

    Google Scholar 

  • Armstrong-James, M., and Millar, J. (1979). Carbon fibre microelectrodes.J. Neurosci. Meth. 1: 279–287.

    Google Scholar 

  • Armstrong-James, M., Fox, K., and Millar, J. (1980). A method for etching the tips of carbon fibre microelectrodes.J. Neurosci. Meth. 2: 431–432.

    Google Scholar 

  • Armstrong-James, M., Caan, A. W., and Fox, K. (1985). Threshold effects of ionotophoresed N-methyl-D aspartate (NMDA) and 2-amino 5 phosphono valeric acid (2APV) on the spontaneous activity of neocortical single neurons in the urethane anesthetized rat.Exp. Brain Res.

  • Ben-Ari, Y., Tremblay, E., Ottersen, O. P., and Naquet, R. (1979). Evidence suggesting secondary epileptogenic lesions after kainic acid: Pretreatment with diazepam prevents distant but not local brain damage.Brain Res. 165: 362–365.

    Google Scholar 

  • Butterworth, R. W. (1982). Neurotransmitter function in thiamine deficient encephalopathy.Neurochem. Int. 4: 449–464.

    Google Scholar 

  • Butterworth, R. W., Giguere, J.-F., and Barbeau, A.-M. (1985). Activities of thiamine dependent enzymes in two experimental models of thiamine defiency encephalopathy. I. The pyruvate dehydrogenase complex.Neurochem. Res. 10: 1417–1428.

    Google Scholar 

  • Butterworth, R. W., Giguere, J.-F., and Barbeau, A.-M. (1986). Activities of thiamine dependent enzymes in two experimental models of thiamine deficiency encephalopathy. 2. Alpha ketoglutarate dehydrogenase.Neurochem. Res. 11: 567–577.

    Google Scholar 

  • Carmichael, E. A., and Stern, R. O. (1931). Korsakoff's syndrome: Its histopathology.Brain 54: 189–213.

    Google Scholar 

  • Chapin, J. K., and Lin, C.-S. (1984). Mapping the body representation of the SI cortex of anesthetized and awake rats.J. Comp. Neurol. 229: 199–213.

    Google Scholar 

  • Collins, R. C., and Olney, J. W. (1982). Focal cortical seizures cause distant thalamic lesions.Science 218: 177–179.

    Google Scholar 

  • Collins, R. C., Kirkpatrick, J. B., and McDougal, D. B. (1970). Some regional pathologic and metabolic consequences in mouse brain of PT-induced thiamine deficiency.J. Neuropath. Exp. Neurol. 29: 57–69.

    Google Scholar 

  • Creutzfelt, O. D., and Houchin, J. (1974). Neuronal basis of EEG waves. In Creutzfeld, O. D. (ed.),Handbook of Electroencephalopathy and Clinical Neurophysiology, Vol. 2, Part C, Elsevier, New York, pp. 5–55.

    Google Scholar 

  • Danbolt, N. C., and Storm-Mathisen, J. (1986). Inhibition by K+ of Na+ dependent aspartate uptake into brain saccules.J. Neurochem. 47: 825–830.

    Google Scholar 

  • Drejer, J., Beneviste, H., Diemer, N. H., and Schousboe, A. (1985). Cellular origin of ischemia-induced glutamate release from brain tissuein vivo andin vitro.J. Neurochem. 45: 145–151.

    Google Scholar 

  • Dreyfus, P. M. (1965). The regional distribution of transketolase in the normal and thiamine deficient nervous system.J. Neuropath. Exp. Neurol. 24: 119–129.

    Google Scholar 

  • Dubner, R., and Wall, P. D. (1972). Somatosensory pathways.Annu. Rev. Physiol. 34: 315–337.

    Google Scholar 

  • Evarts, E. V. (1961). Effects of sleep and waking on spontaneous and evoked discharge of single units in visual cortex.Fed. Proc. 19: 828–837.

    Google Scholar 

  • Evarts, E. V., Bental, E., Bihari, B., and Huttenlocker, P. R. (1962). Spontaneous discharge of single neurons during sleep and waking.Science 135: 726–728.

    Google Scholar 

  • Fox, K., and Armstrong-James, M. (1986). The role of the anterior intralaminar nuclei and N-methyl-D aspartate receptors in spontaneous burst generation of rat neocortical neurons.Exp. Brain Res. 63: 505–518.

    Google Scholar 

  • Fox, K., Armstrong-James, M., and Millar, J. (1980). Electrical properties of carbon fiber microelectrodes.J. Neurosci. Meth. 3: 37–48.

    Google Scholar 

  • Gaitonde, M. K., Nixey, R. W. K., and Sharman, I. M. (1974). The effect of deficiency of thiamine on the metabolism of [U14C] glucose and [U14C] ribose and the levels of amino acids in rat brain.J. Neurochem. 22: 53–61.

    Google Scholar 

  • Gibson, G. E., Ksiezak-Reding, H., Sheu, K. F. R., Mykytyn, V., and Blass, J. P. (1984). Correlation of enzymatic, metabolic, and behavior defects in thiamine deficiency and its reversal.Neurochem. Res. 9: 803–814.

    Google Scholar 

  • Giguere, J.-F., and Butterworth, R. W. (1987). Activities of thiamine dependent enzymes in two experimental models of thiamine deficiency encephalopathy. 3. Transketolase.Neurochem. Res. 12: 305–310.

    Google Scholar 

  • Glenn, L. L., and Steriade, M. (1982). Discharge rate and exitability of cortically projecting neurons in the intralaminar nuclei during waking and sleep rates.J. Neurosci. 2: 1387–1404.

    Google Scholar 

  • Graff-Radford, N. R., Damasio, H., Yamada, T., Eslinger, P. J., and Damasio, A. R. (1985). Nonhaemorrhagic thalamic infarction.Brain 108: 455–516.

    Google Scholar 

  • Gubler, C. J. (1968). Enzyme studies in thiamine deficiency.Int. J. Vitamin Res. 38: 287–303.

    Google Scholar 

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

    Google Scholar 

  • Hakim, A. M. (1986). Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat.J. Cerebral Blood Flow Metab. 6: 79–85.

    Google Scholar 

  • Hakim, A. M., and Pappius, H. M. (1981). The effect of thiamine deficiency on local cerebral glucose utilization.Ann. Neurol. 9: 334–339.

    Google Scholar 

  • Hakim, A. M., and Pappius, H. M. (1983). Sequence of metabolic, clinical and histological events in experimental thiamine deficiency.Ann. Neurol. 13: 365–375.

    Google Scholar 

  • Hamel, E., Butterworth, R. W., and Barbeau, A. (1979). Effect of thiamine deficiency on levels of putative amino acid transmitters in affected regions of the rat brain.J. Neurochem. 33: 575–577.

    Google Scholar 

  • Hansen, A. J., and Zeuthen, T. (1981). Extracellular ion concentration during spreading depression and ischemia in the rat brain cortex.Acta Physiol. Scand. 113: 437–445.

    Google Scholar 

  • Herkenham, M. (1980). Laminar organization of thalamic projections to rat neocortex.Science 207: 532–534.

    Google Scholar 

  • Holmes, O., and Houchin, J. (1966). Units in the cerebral cortex of the anesthetized rat and the correlations between their discharges.J. Physiol. 187: 651–671.

    Google Scholar 

  • Hubel, D. H. (1959). Single unit activity in the striate cortex of unanesthetized cats.J. Physiol. 147: 226–238.

    Google Scholar 

  • Irlc, E., and Markowitsch, H. J. (1982). Thiamine deficiency in the cat leads to severe learning deficits and widespread neuroanatomical damage.Exp. Brain Res. 48: 199–208.

    Google Scholar 

  • Irle, E., and Markowtisch, H. J. (1983). Widespread neuroanatomical damage and learning deficits following chronic alcohol consumption or vitamin B-1 (thiamine) deficiency in rats.Behav. Brain Res. 9: 277–294.

    Google Scholar 

  • Jacobowtiz, D. M., and Creed, G. J. (1983). Cholinergic projection sites of the nucleus of tractus diagonalis.Brain Res Bull. 10: 365–371.

    Google Scholar 

  • Joh, T. H., and Ross, M. E. (1983). Immunocytochemistry.Meth. Neurosci. 3: 121–138.

    Google Scholar 

  • Kase, C. S., and Mohr, J. P. (1986). Supratentorial intracerebral hemorrhage. In Barnett, H. J. M., Mohr, J. P., Stein, B. M., and Yatsu, F. M. (eds.),Stroke: Pahtophysiology, Diagnosis, and Management, Vol. 1, Curchill Livingstone, New York, pp. 525–547.

    Google Scholar 

  • Koelle, G. B. (1955). The histochemical identification of acetylcholinesterase in cholinergic adrenergic sensory neurons.J. Pharmacol. Exp. Ther. 114: 167–184.

    Google Scholar 

  • Langlais, P. J. (1985).Behavioral, anatomical, and Neurochemical Defecits Following a Bout of Thiamine Deficiency in the Rat, Ph.D. thesis Northeastern University, Boston, pp. 1–33.

    Google Scholar 

  • Langlais, P. J., Mair, R. G., Anderson, C. D., and McEntee, W. J. (1986). Thalamic lesions and regional brain monoaminergic alterations following an acute bout of thiamine deficiency in the rat.Soc. Neurosci. Abstr. 12: 751.

    Google Scholar 

  • Leavitt, P., and Rakic, P. (1980). Immunoperoxidase location of glial fibrillary acidic protein in radial glial cells and astroglia of the developing rhesus monkey brain.J. Comp. Neurol. 193: 815–840.

    Google Scholar 

  • Mair, R. G., Anderson, C. D., and Langlais, P. J. (1986). Evidence for spatial memory deficits in the rat following recovery from a bout of thiamine deficiency.Soc. Neurosci. Abstr. 12: 745.

    Google Scholar 

  • Morison, R. S., and Dempsey, E. W. (1942). A study of thalamocortical relations.Am. J. Physiol. 135: 281–292.

    Google Scholar 

  • Moruzzi, G. (1963). Active processes in the brainstem during sleep.Harvey Led,58: 233–297.

    Google Scholar 

  • Mugnaini, E., Oertel, W. H., Schmechel, D. E., Tappaz, M. L., and Kopin, I. J. (1982). The immunocytochemical demonstration of gamma-aminobutyric acid neurons. InCytochemical Methods in Neuroanatomy, Alan R. Liss, New York, pp. 297–329.

    Google Scholar 

  • Olney, J. W. (1978). Neurotoxicity of excitatory amino acids. In McGeer, E. G., Olney, J. W., and McGeer, P. L. (eds.),Kainic Acid as a Tool in Neurobiology, Raven Press, New York, pp. 95–121.

    Google Scholar 

  • Olney, J. W. (1984). Excitotoxins: An overview. In Fuxe, K., Roberts, P., and Schwarcz, R. (eds.)Excitotoxins, pp. 82–96.

  • Olney, J. W., Rhee, V., and Ho, O. L. (1974). Kainic acid: A powerful analog of glutamate.Brain Res. 77: 507–512.

    Google Scholar 

  • Park, J. K., Joh, T. H., and Ebner, F. F. (1986). Tyrosine hydroxylase is expressed by neocortical neurons after transplantation.Proc. Natl. Acad. Sci. 83: 7495–7498.

    Google Scholar 

  • Paxinos, G., and Watson, C. (1982).The Rat Brain in Stereotaxic Coordinates, Academic Press, New York.

    Google Scholar 

  • Peters, R. A. (1967). The biochemical lesion in thiamine deficiency. InThiamine DEficiency CIBA Foundation Study Group Vol. 8, Little, Brown, Boston, pp. 1–8.

    Google Scholar 

  • Pincus, J. H., and Wells, K. (1972). Regional distribution of thiamine dependent enzymes in normal and thiamine deficient brain.Exp, Neurol. 37: 495–501.

    Google Scholar 

  • Plaitakis, A., Niklas, W. J., and Berl, S. (1979). Alterations in uptake and metabolism of aspartate and glutamate in brain of thiamine deficient animals.Brain Res. 171: 489–502.

    Google Scholar 

  • Rieke, G. K. (1987). Thalamic arterial pattern: An endocast and scanning electron microscopic study in normotensive rats.Am. J. Anat. 178: 45–54.

    Google Scholar 

  • Rieke, G. K., and Cannon, M. S. (1985). A histochemical study of cerebral cortical vessies and ganglionic vessels of the caudatoputamen in aging normotensive rats.Stroke 16: 285–292.

    Google Scholar 

  • Rindi, G., and Perri, V. (1968). Uptake of pyrithiamine by tissue of rats.Biochem. J. 80: 214–216.

    Google Scholar 

  • Ross, D. T., and Ebner, F. F. (1985). A comparison of thalamic retrograde degeneration induced by cortical ablation and intracortical kainic acid injection.Anat. Rec. 211: 164a.

    Google Scholar 

  • Ross, D. T., and Ebner, F. F. (1986). Increased excitability of thalamic relay neurons in the ventrobasal complex following ablation of the SI cortex in the adult rat.Soc. Neurosci. Abstr. 12: 983.

    Google Scholar 

  • Schwob, J. E., Fuller, T., Price, J. L., and Olney, J. W. (1980). Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: An histological study.Neuroscience 5: 991–1014.

    Google Scholar 

  • Simon, R. P., Swan, J. H., Griffiths, J. H., and Meldrum, B. S. (1984). Blockade of N-methylaspartate receptors may protect against ischemie damage in the brain.Science 226: 850–852.

    Google Scholar 

  • Steriade, M., and Hobson, J. A. (1976). Neuronal activity during the sleep-wake cycle.Prog. Neurobiol. 6: 155–376.

    Google Scholar 

  • Thompson, S. G., and McGeer, E. G. (1985). GABA transaminase and glutamic acid decarboxylase changes in the brain of rats treated with pyrithiamine.Neurochem. Res. 10: 1653–1660.

    Google Scholar 

  • Troncoso, I. C., Johnston, M. W., Hess, K. M., Griffin, J. W., and Price, D. L. (1981). Model of Wernicke's encephalopathy.Arch. Neurol. 8: 350–354.

    Google Scholar 

  • Utterback, R. A. (1977). Hemorrhagic cerebrovascular disease. In Baker, B. S., and Baker, L. H. (eds.),Clinical Neurology, Vol. 1, Harper and Row, Hagerstown, Md, Ch. 11.

    Google Scholar 

  • Victor, M., Adams, R. D., and Collins, G. H. (1971).The Wernicke-Korsakoff Syndrome, 1st ed., F. A. Davis, Philadelphia. Vorhees, C. V., Schmidt, D. E., Barrett, R. J., and Schenkner, S. (1977). Effects of thiamine deficiency upon acetylcholine levels and uptake in vivo in rat brain.J. Nutr. 107: 1902–1908.

    Google Scholar 

  • Waite, P. M. E. (1973). The responses of cells in the rat thalamus to mechanical movements of the whiskers.J. Physiol. 228: 541–561.

    Google Scholar 

  • Watanabe, I. (1978). Early edematous lesions fo pyrithiiamine induced acute thiamine deficient encephalopathy in the mouse.J. Neuropath. Exp. Neurol. 37: 401–413.

    Google Scholar 

  • Watanabe, I. (1981a). Edematous necrosis in thiamine-deficient encephalopathy of the mouse.J. Neuropath. Exp. Neurol. 40: 454–471.

    Google Scholar 

  • Watanabe, I. (1981b). Hemorrhages of thiamine deficient encephalopathy.J. Neuropath. Exp. Neurol. 40: 566–580.

    Google Scholar 

  • Watanabe, I. (1985). Experimental thiamine deficiency encephalopathy of the mouse and rat. In Adachi, M., Hirano, A., and Aronson, S. M. (eds.),The Pathology of the Myelinated Axon, Igaku-Shoin, New York.

    Google Scholar 

  • Welker, C. (1971). Microelectrode delineation of fine grain somatotopic organization of Sml cerebral neocortex in albino rat.Brain Res. 26: 259–275.

    Google Scholar 

  • Wise, S. P., and Jones, E. G. (1976). Developmental studies of thalamocortical and commisural connections in the rat somatic sensory cortex.J. Comp. Neurol. 178: 187–208.

    Google Scholar 

  • Witt, E. D., and Goldman-Rakic, P. S. (1983). Intermittent thiamine deficiency in the rhesus monkey. I. Progression of neurological signs and neuroanatomical lesions.Ann. Neurol. 13: 376–395.

    Google Scholar 

  • Yamori, Y., Horie, R., Handa, H., Sato, M., and Fukase, M. (1976). Pathogenic similarity of strokes in stroke prone spontaneously hypertensive rats and humans.Stroke 7: 46–53.

    Google Scholar 

  • Yamori, Y., Horie, R., Akiguchi, I., Nara, Y., Ohtaka, M., and Fukase, M. (1977). Pathogenic mechanisms and prevention of stroke in stroke prone spontaneously hypertensive rats. In DeJong, W., Provost, A. P., and Shapiro, A. P. (eds.),Progress in Brain Research 47: Hypertension and Brain Mechanism, Elsevier, New York, pp. 219–234.

    Google Scholar 

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Authors and Affiliations

  1. Neurophysiology Section, Physiology Department, London Hospital Medical College, London University, El 2AD, London, England

    M. Armstrong-James

  2. Department of Clinical Neuroscience, Rhode Island Hospital, Brown University, 02902, Providence, Rhode Island

    D. T. Ross

  3. Center for Neural Science, Brown University, 02912, Providence, Rhode Island

    F. Chen

  4. Neurobiology Section, Division of Biology and Medicine, Brown University, 02912, Providence, Rhode Island

    F. F. Ebner

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Armstrong-James, M., Ross, D.T., Chen, F. et al. The effect of thiamine deficiency on the structure and physiology of the rat forebrain. Metab Brain Dis 3, 91–124 (1988). https://doi.org/10.1007/BF01001012

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