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Disease relevance of Hibernation


Psychiatry related information on Hibernation

  • This study compared the survival of human fetal striatal tissue that had been stored for 24 h in a defined hibernation medium with that of fresh human fetal striatal tissue following xenotransplantation in a rat model of Huntington's disease (HD) [6].
  • Androgen levels were undetectable in torpid squirrels, elevated in animals sampled during periodic arousals, and elevated in most males within 3 weeks after terminating hibernation [7].
  • Thus animals emerging from the hypometabolic states of hibernation or daily torpor exhibit an increase in SWA akin to sleep deprivation [8].

High impact information on Hibernation

  • Circannual control of hibernation by HP complex in the brain [9].
  • In this study, we used a combination of 13C-NMR spectroscopy, GC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-13C]glucose during a 3-4-h period of acute ischemic hibernation [10].
  • Here, we report that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme 4 are up-regulated in the heart during hibernation [11].
  • The results indicate that persistence of vasopressin release in the lateral septum of the European hamster during winter can prevent hibernation [12].
  • Nitric oxide and short-term hibernation: friend or foe [13]?

Chemical compound and disease context of Hibernation


Biological context of Hibernation


Anatomical context of Hibernation


Associations of Hibernation with chemical compounds

  • In this study, we show that histamine neuronal systems undergo major changes during hibernation that are consistent with such a role [29].
  • To evaluate how the activity of a well-established neurotransmitter pathway is modulated by a behavioral state, 3H-spiperone binding sites and dopamine (DA) and DA metabolite concentrations were measured in the striata of ground squirrels in 5 phases of the hibernation cycle [19].
  • The tissue levels of histamine and its first metabolite tele-methylhistamine were also elevated throughout the brain of hibernating animals, suggesting an increase in histamine turnover during hibernation, which occurs without an increase in histidine decarboxylase mRNA expression [29].
  • The MVF was higher where both thallium and MRI predicted hibernation (0.77+/-0.07) than in segments predicted by thallium alone (0.69+/-0.13, p < 0.05) [30].
  • RESULTS: Thallium was most sensitive in predicting hibernation (88%) and MRI most specific (84%); and, although there was good agreement between thallium and tetrofosmin (85%), agreement between MRI and thallium (59%) or tetrofosmin (59%) was poor [30].

Gene context of Hibernation

  • Activities of ERK-activated kinases also responded to hibernation: MAPKAPK-1 rose in muscle and brain, MAPKAPK-2 decreased in liver and kidney but rose in the other three organs, and p70S6K kinase activity decreased kidney and heart [31].
  • ERK1/2 activities increased significantly in muscle and brain during hibernation but decreased in kidney and liver [31].
  • The objective of this study was to evaluate the effects on fetal dopaminergic tissue of GDNF-supplemented hibernation for extended periods of 6 to 15 days [32].
  • Here we report significant increases in mRNA levels for Ucp2 in WAT (1. 6-fold) and Ucp3 in skeletal muscle (3-fold) during hibernation [33].
  • These results indicate the potential for a role of UCP2 and UCP3 in thermal homeostasis during hibernation and indicate that parallel mechanisms and multiple tissues could be important for nonshivering thermoregulation in mammals [33].

Analytical, diagnostic and therapeutic context of Hibernation


  1. Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and inotropic stimulation. Schulz, R., Rose, J., Martin, C., Brodde, O.E., Heusch, G. Circulation (1993) [Pubmed]
  2. Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels. Prendergast, B.J., Freeman, D.A., Zucker, I., Nelson, R.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2002) [Pubmed]
  3. Homeostatic versus circadian effects of melatonin on core body temperature in humans. Cagnacci, A., Kräuchi, K., Wirz-Justice, A., Volpe, A. J. Biol. Rhythms (1997) [Pubmed]
  4. Classical pathway serum complement activity throughout various stages of the annual cycle of a mammalian hibernator, the golden-mantled ground squirrel, Spermophilus lateralis. Maniero, G.D. Dev. Comp. Immunol. (2002) [Pubmed]
  5. Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels. Ma, Y.L., Zhu, X., Rivera, P.M., Tøien, Ø., Barnes, B.M., LaManna, J.C., Smith, M.A., Drew, K.L. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  6. Hibernated human fetal striatal tissue: successful transplantation in a rat model of Huntington's disease. Hurelbrink, C.B., Armstrong, R.J., Barker, R.A., Dunnett, S.B., Rosser, A.E. Cell transplantation. (2000) [Pubmed]
  7. Annual cycles of gonadotropins and androgens in the hibernating golden-mantled ground squirrel. Barnes, B.M. Gen. Comp. Endocrinol. (1986) [Pubmed]
  8. From slow waves to sleep homeostasis: new perspectives. Borbély, A.A. Archives italiennes de biologie. (2001) [Pubmed]
  9. Circannual control of hibernation by HP complex in the brain. Kondo, N., Sekijima, T., Kondo, J., Takamatsu, N., Tohya, K., Ohtsu, T. Cell (2006) [Pubmed]
  10. Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia. McNulty, P.H., Sinusas, A.J., Shi, C.Q., Dione, D., Young, L.H., Cline, G.C., Shulman, G.I. J. Clin. Invest. (1996) [Pubmed]
  11. Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating mammal. Andrews, M.T., Squire, T.L., Bowen, C.M., Rollins, M.B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  12. Central vasopressin infusion prevents hibernation in the European hamster (Cricetus cricetus). Hermes, M.L., Buijs, R.M., Masson-Pévet, M., van der Woude, T.P., Pévet, P., Brenklé, R., Kirsch, R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  13. Nitric oxide and short-term hibernation: friend or foe? Canty, J.M. Circ. Res. (2000) [Pubmed]
  14. Reverse flux through cardiac NADP(+)-isocitrate dehydrogenase under normoxia and ischemia. Comte, B., Vincent, G., Bouchard, B., Benderdour, M., Des Rosiers, C. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  15. Glucose uptake increases relative to oxygen consumption during short-term hibernation. McFalls, E.O., Baldwin, D.R., Marx, D., Maxwell, K., Ward, H.B. Basic Res. Cardiol. (2000) [Pubmed]
  16. Time-course of blood acid-base state during arousal from hibernation in the European hamster. Malan, A., Mioskowski, E., Calgari, C. J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. (1988) [Pubmed]
  17. Suppression of annual plasma testosterone and thyroxine cycles in the edible dormouse Glis glis under constant photoperiod at 24 degrees C. Jallageas, M., Assenmacher, I. Experientia (1986) [Pubmed]
  18. Role of norepinephrine in development of short-term myocardial hibernation. Fu, Z.L., Feng, Y.B., Xu, H.X., Zhang, X.P., Shi, C.Z., Gu, X. Acta Pharmacol. Sin. (2006) [Pubmed]
  19. Modulation of activity of the striatal dopaminergic system during the hibernation cycle. Kilduff, T.S., Bowersox, S.S., Faull, K.F., Zeller-DeAmicis, L., Radeke, C.M., Ciaranello, R.D., Heller, H.C., Barchas, J.D., Dement, W.C. J. Neurosci. (1987) [Pubmed]
  20. Stimulation of tyrosine phosphorylation of a brain protein by hibernation. Ohtsuki, T., Jaffe, H., Brenner, M., Azzam, N., Azzam, R., Frerichs, K.U., Hallenbeck, J.M. J. Cereb. Blood Flow Metab. (1998) [Pubmed]
  21. Seasonal variation and the influence of body temperature on plasma concentrations and binding of thyroxine and triiodothyronine in the woodchuck. Young, R.A., Danforth, E., Vagenakis, A.G., Krupp, P.P., Frink, R., Sims, E.A. Endocrinology (1979) [Pubmed]
  22. Myocardial adaptation during acute hibernation: mechanisms of phosphocreatine recovery. Schaefer, S., Carr, L.J., Kreutzer, U., Jue, T. Cardiovasc. Res. (1993) [Pubmed]
  23. Freeze tolerance in the wood frog Rana sylvatica is associated with unusual structural features in insulin but not in glucagon. Conlon, J.M., Yano, K., Chartrel, N., Vaudry, H., Storey, K.B. J. Mol. Endocrinol. (1998) [Pubmed]
  24. Changes in hippocampal histamine receptors across the hibernation cycle in ground squirrels. Sallmen, T., Lozada, A.F., Anichtchik, O.V., Beckman, A.L., Leurs, R., Panula, P. Hippocampus. (2003) [Pubmed]
  25. ATP gated potassium channels in acute myocardial hibernation and reperfusion. Offstad, J., Kirkebøen, K.A., Ilebekk, A., Downing, S.E. Cardiovasc. Res. (1994) [Pubmed]
  26. Enhanced vasoconstrictor responses in renal and femoral arteries of the golden hamster during hibernation. Karoon, P., Knight, G., Burnstock, G. J. Physiol. (Lond.) (1998) [Pubmed]
  27. Changes in the form of Arrhenius plots of the activity of glucagon-stimulated adenylate cyclase and other hamster liver plasma-membrane enzymes occurring on hibernation. Houslay, M.D., Palmer, R.W. Biochem. J. (1978) [Pubmed]
  28. Control of plasma sex steroid-binding protein (SBP) in the little brown bat: effects of thyroidectomy and treatment with L- and D-thyroxine on the induction of SBP in adult males. Damassa, D.A., Gustafson, A.W., Kwiecinski, G.G., Pratt, R.D. Biol. Reprod. (1985) [Pubmed]
  29. Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation. Sallmen, T., Beckman, A.L., Stanton, T.L., Eriksson, K.S., Tarhanen, J., Tuomisto, L., Panula, P. J. Neurosci. (1999) [Pubmed]
  30. The histology of viable and hibernating myocardium in relation to imaging characteristics. Gunning, M.G., Kaprielian, R.R., Pepper, J., Pennell, D.J., Sheppard, M.N., Severs, N.J., Fox, K.M., Underwood, S.R. J. Am. Coll. Cardiol. (2002) [Pubmed]
  31. Mitogen-activated protein kinases and selected downstream targets display organ-specific responses in the hibernating ground squirrel. MacDonald, J.A., Storey, K.B. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  32. Glial cell line-derived neurotrophic factor-supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage. Hebb, A.O., Hebb, K., Ramachandran, A.C., Mendez, I. J. Neurosurg. (2003) [Pubmed]
  33. Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels. Boyer, B.B., Barnes, B.M., Lowell, B.B., Grujic, D. Am. J. Physiol. (1998) [Pubmed]
  34. Seasonal variation in thyrotropin-releasing hormone (TRH) content of different brain regions and the pineal in the mammalian hibernator, Citellus lateralis. Stanton, T.L., Winokur, A., Beckman, A.L. Regul. Pept. (1982) [Pubmed]
  35. Differential regulation of glomerular and interstitial endothelial nitric oxide synthase expression in the kidney of hibernating ground squirrel. Sandovici, M., Henning, R.H., Hut, R.A., Strijkstra, A.M., Epema, A.H., van Goor, H., Deelman, L.E. Nitric Oxide (2004) [Pubmed]
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