Metabolic Brain Disease

, Volume 13, Issue 3, pp 225–239

Thiamine Deficiency-Induced Disruptions in the Diurnal Rhythm and Regulation of Body Temperature in the Rat

  • P.J. Langlais
  • T. Hall


In the present study, diurnal rhythm and regulation of body temperature were monitored during and several weeks following pyrithiamine-induced thiamine deficiency (PTD group, n=8) or pairfeeding (control group, n=9). A significant decline of core body temperature and a disruption of its diurnal rhythm were observed at varying stages of PTD treatment. Following thiamine administration and return to thiamine-fortified chow, body temperature continued to fall and several days transpired before body temperature and its diurnal rhythm were returned to normal. When exposed to warm and cold environments, no significant group differences were observed in either the maximum temperature change or the time elapsed to reach maximal temperature change. Histological examination revealed necrotic lesions in thalamus and mammillary body in the PTD group characteristic of Wernicke's encephalopathy. No significant damage was observed in the medial preoptic and suprachiasmatic nuclei, brain regions involved in the regulation of body temperature and circadian rhythm. These findings suggest that hypothermia and disruption of the diurnal rhythm of body temperature can be reversed by restoration of adequate thiamine levels and are related to biochemical and physiological disturbances rather than gross structural changes.

Thiamine deficiency diurnal rhythm body temperature hypothalamic nuclei rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baum, R.A. and Iber, F.L. (1984). Thiamin-the interaction of aging, alcoholism, and malabsorption in various populations. World Rev. Nutr. Diet 44:85–116.PubMedGoogle Scholar
  2. Butterworth, R.F. and Besnard, A.M. (1990). Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer's disease. Metab. Brain Dis. 5:179–184.PubMedGoogle Scholar
  3. Clark, W.G. and Clark, L.D. (1980). Changes in body temperature after administration of acetylcholine, histamine, morphine, prostaglandins and related agents. Neurosci. Biobehav. Rev. 4:175–240.CrossRefPubMedGoogle Scholar
  4. Crespi, F. and Jouvet, M. (1982). Sleep and indolamine alterations induced by thiamine deficiency. Brain Res. 248:275–283.CrossRefPubMedGoogle Scholar
  5. Donnan, G.A. and Seeman, E. (1980). Coma and hypothermia in Wernicke's encephalopathy. Aust. N.Z. J. Med. 10:438–439.PubMedGoogle Scholar
  6. Diamond, P. and LeBlanc, J. (1987). Role of autonomic nervous system in postprandial thermogenesis in dogs. Am. J. Physiol. 252:E719–726.PubMedGoogle Scholar
  7. Fishbeck, K.H. and Simon, R.P. (1981). Neurological manifestations of accidental hypothermia. Ann. Neurol. 10:384–387.PubMedGoogle Scholar
  8. Gallaher, E.J., Enger, D.A. and Swen, J.W. (1985). Automated remote temperature measurement in small animals using a telemetry-microcomputer interface. Computer Biological Medicine 15:103–110.CrossRefGoogle Scholar
  9. Geny, C., Pradat, P.F., Yulis, J., Walter, S., Cesaro, D., and Degos, J.D. (1992). Hypothermia, Wernicke encephalopathy and multiple sclerosis. Acta Neurologica Scandinavia 86:632–634.Google Scholar
  10. Gibson, G.E., Sheu, K.-F.R., Baker, A.C., Carlson, K.C., Harding, D., Perrino, P. and Blass, J.P. (1988). Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of Alzheimer patients. Arch. Neurol. 45:836–840.PubMedGoogle Scholar
  11. Gordon, C.J. (1990). Thermal biology of the laboratory rat. Physiology and Behavior, 47:963–991.CrossRefPubMedGoogle Scholar
  12. Gordon, C.J. (1993). Temperature Regulation in Laboratory Rodents. Cambridge Univ. Press, New York, pp. 111–112.Google Scholar
  13. Green, M.D., Cox, B., and Lomax, P. (1976). Histamine H1-and H2-receptors in the central thermoregulatory pathway of the rat. J. Neurosci. Res. 1:353–359.Google Scholar
  14. Hakim, A.M. (1984). The induction and reversibility of cerebral acidosis in thiamine deficiency. Ann. Neurol. 16:673–679.PubMedGoogle Scholar
  15. Hakim, A.M. and Pappius, H.M. (1983). Sequence of metabolic, clinical, and histological events in experimental thiamine deficiency. Ann. Neurol. 13:365–375.PubMedGoogle Scholar
  16. Harper, C.G. (1979). Wernicke's encephalopathy: A more common disease than realized. J. Neurol. Neurosurg. Psychiat. 42:226–231.PubMedGoogle Scholar
  17. Harper, C.G., Giles, M.I, and Finlay-Jones, R. (1986). Clinical signs in the Wernicke-Korsakoff complex—a retrospective analysis of 131 cases diagnosed at autopsy. J. Neurol. Neurosurg. Psychiat. 49:341–345.PubMedGoogle Scholar
  18. Harper, C.G., Gold, J., Rodriguez, M., and Perdices, M. (1989). The prevalence of the Wernicke-Korsakoff syndrome in Sydney, Australia: A prospective necropsy study. J. Neurol. Neurosurg. Psychiat. 52:282–285.PubMedGoogle Scholar
  19. Jernigan, T.L., Schafer, K., Butters, N., and Cermak, L.S. (1991). Magnetic resonance imaging of alcoholic Korsakoff patients. Neuropsychopharmacol. 4:175–186.Google Scholar
  20. Kearsley, J.H. and Musso, A.F. (1980). Hypothermia and coma in the Wernicke-Korsakoff syndrome. Med. J. Aust. 2:504–506.PubMedGoogle Scholar
  21. Langlais, P.J., Mandel, R.J., and Mair, R.G. (1992). Diencephalic lesions, learning impairments, and intact retrograde memory following acute thiamine deficiency in the rat. Behav. Brain Res. 48:177–185.PubMedGoogle Scholar
  22. Langlais, P.J., Zhang, S.X., Weilersbacher, G., Hough, L.B., and Barke, K.E. (1994). Histamine-mediated neuronal death in a rat model of Wernicke's encephalopathy. J. Neurosci. Res. 38:565–574.PubMedGoogle Scholar
  23. LeRoch, K.L., Riche, D., and Sara, S. (1987). Persistence of habituation deficits after neurological recovery from severe thiamine deficiency. Behav. Brain Res. 26:37–46.CrossRefPubMedGoogle Scholar
  24. Liang, C.C. (1975). Metabolic changes in rats during developing thiamine deficiency. Biochem. J. 146:739–740.PubMedGoogle Scholar
  25. Lipton, J.M., Dwyer, P.E., and Fossler, D.E. (1974). Effects of brainstem lesions on temperature regulation in hot and cold environments. Am. J. Physiol. 226:356–365.Google Scholar
  26. Lipton, J.M., Payne, H., Garza, H.R., and Rosenberg, R.N. (1978). Thermolability in Wernicke's encephalopathy. Arch. Neurol. 35:750–753.PubMedGoogle Scholar
  27. Mann, M.W., and Degos, J.D. (1987). L'hypothermie dans l'encephalopathie de Wernicke. Rev. Neurol. 143:684–686.PubMedGoogle Scholar
  28. Martin, P.R., Higa, S., Burns, S., Tamarkin, L., Ebert, M.H., and Markey, S.P. (1984). Decreased 6-hydroxymelatonin excretion in Korsakoff's psychosis. Neurol. 34:966–968.Google Scholar
  29. Martin, P.R., Loewenstein, R.J., Kaye, W.H., Ebert, M.H., Weingartner, H., and Gillin, J.C. (1986). Sleep EEG in Korsakoff's psychosis and Alzheimer's disease. Neurol. 36:411–4.Google Scholar
  30. Mochizuki, T., Yamatodani, A., Okakura, K., Horii, A., Inagaki, N., and Wada, H. (1992). Circadian rhythm of histamine release from the hypothalamus of freelymoving rats. Physiol. and Behav. 51:391–394.CrossRefGoogle Scholar
  31. Onodera, K., Shinoda, H., and Watanabe, T. (1990). Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats. Japan J. Pharmacol. 54:339–343.Google Scholar
  32. O'Rourke, N.P., Bunker, V.W., Thomas, A.J., Finglas, P.M., Bailey, A.L., and Clayton, B.E. (1990). Thiamine status of healthy and institutionalized elderly subjects: analysis of dietary intake and biochemical indices. Age and Aging 19:325–329.Google Scholar
  33. Osborne, A.R. and Refinetti, R. (1995). Effects of hypothalamic lesions on the body temperature rhythm of the golden hamster. Neuroreport 6:2187–92.PubMedGoogle Scholar
  34. Parker, W.D., Haas, R., Stumpf, D.A., Parks, J., Eguren, L.A. and Jackson, C. (1984). Brain mitochrondrial metabolism in experimental thiamine deficiency. Neurology 34:1477–1481.PubMedGoogle Scholar
  35. Philip, G. and Smith, J.F. (1973). Hypothermia and Wernicke's Encephalopathy. Lancet ii:122–124.CrossRefGoogle Scholar
  36. Plaitakis, A., Nicklas, W.J., and Berl, S. (1978). Thiamine deficiency: Selective impairment of the cerebellar serotonergic system. Neurol. 28:691–698.Google Scholar
  37. Plaitakis A, Berl., S., and Tamir, H. (1981). Thiamine deficiency: effect on serotonin binding protein in rat hypothalamus. Brain Research 217:416–419.CrossRefPubMedGoogle Scholar
  38. Schwenk, J., Gosztonyi, A., Thierauf, P., Iglesias, J., and Langer, E. (1990). Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome. J. Neurol. 237:445–447.CrossRefPubMedGoogle Scholar
  39. Sharp, F.R., Bolger, E., and Evans, K. (1982). Thiamine deficiency limits glucose utilization and glial proliferation in brain lesions of symptomatic rats. J. Cereb. Blood Flow Metab. 2:203–207.PubMedGoogle Scholar
  40. Smith, D.K., Ovesen, L., Chu, R., Sackel, S., and Howard, L. (1983). Hypothermia in a patient with Anorexia Nervosa. Metabolism 2:1151–1154.CrossRefGoogle Scholar
  41. Torvik, A., Lindboe, C.F., and Rogde, S. (1982). Brain lesions in alcoholics: A neuropathological study with clinical correlations. J. Neurol. Sci. 56:233–248.CrossRefPubMedGoogle Scholar
  42. Troncoso, J.C., Johnston, M.V., Hess, K.M., Griffin, J.W., and Price, D.L. (1981). Model of Wernicke's encephalopathy. Arch. Neurol. 38:350–354.PubMedGoogle Scholar
  43. Tuomisto, L. (1991). Involvement of histamine in circadian and other rhythms. In: (T. Watanabe and H. Wada, eds.) Histaminergic Neurons: Morphology and Function. CRC Press, Boca Raton, pp. 283–295Google Scholar
  44. Turek, F.W. (1985). Circadian neural rhythms in mammals. Ann. Rev. Physiol. 47:49–64.CrossRefGoogle Scholar
  45. Victor, M., Adams, R.D., and Collins, G.H. (1989). The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. F.A Davis, Philadelphia. pp.39–52Google Scholar
  46. Vortmeyer, A.O., and Colmant, H.J. (1988). Differentiation between brain lesions in experimental thiamine deficiency. Virchows Archive A Pathol. Anat. 414:61–67.Google Scholar
  47. Wada, H., Watanabe, T., Yamatodani, A., Maeyama, K., Itoi, K., Cacaberos, L. et al. (1985). Physiological functions of histamine in the brain. In: (C.R. Ganellin and J.C. Schwartz, eds.) Advances in Biosciences, Vol. 51, Frontiers in Histamine Research, pp. 225–235, Pergamon Press, Oxford.Google Scholar
  48. Wallis, W.E., Willoughby, E., and Baker, P. (1978). Coma in the Wernicke-Korsakoff syndrome. Lancet 2:400–401.CrossRefPubMedGoogle Scholar
  49. Watanabe, I. (1978). Pyrithiamine-induced acute thiamine-deficient encephalopathy in the mouse. Exp. Molec. Pathol. 28:381–394.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • P.J. Langlais
    • 1
    • 2
  • T. Hall
    • 2
  1. 1.Neurology ResearchVA Medical Center/UCSD Sch Med.San Diego
  2. 2.Department of PsychologySan Diego State UniversityU.S.A

Personalised recommendations