Mammalian hibernation: a unique model for medical research

Xin Xing, Shiqiang Wang

PDF(244 KB)
PDF(244 KB)
Frigid Zone Medicine ›› 2021, Vol. 1 ›› Issue (2) : 65-68. DOI: 10.2478/fzm-2021-0008
REVIEW

Mammalian hibernation: a unique model for medical research

Author information +
History +

Abstract

Hibernation is an adaptive behavior for some small animals to survive cold winter. Hibernating mammals usually down-regulate their body temperature from ~37°C to only a few degrees. During the evolution, mammalian hibernators have inherited unique strategies to survive extreme conditions that may lead to disease or death in humans and other non-hibernators. Hibernating mammals can not only tolerant deep hypothermia, hypoxia and anoxia, but also protect them against osteoporosis, muscle atrophy, heart arrhythmia and ischemia-reperfusion injury. Finding the molecular and regulatory mechanisms underlying these adaptations will provide novel ideas for treating related human diseases.

Keywords

hibernation / deep hypothermia / hypoxia / osteoporosis / muscle atrophy / arrhythmia / ischemia-reperfusion

Cite this article

Download citation ▾
Xin Xing, Shiqiang Wang. Mammalian hibernation: a unique model for medical research. Frigid Zone Medicine, 2021, 1(2): 65‒68 https://doi.org/10.2478/fzm-2021-0008

References

[[1]]
Andrews M T. Advances in molecular biology of hibernation in mammals. Bioessays, 2007; 29(5): 431-440.
[[2]]
Carey H V, Andrews M T, Martin S L. Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev, 2003; 83(4): 1153-1181.
[[3]]
Lyman C, Willis J, Malan A, et al. Hibernation and torpor in mammals and birds. New York: Academic press, 1982.
[[4]]
Yang M, Xing X, Guan S, et al. Hibernation patterns and changes of body temperature in Daurian ground squirrels (Spermophilus dauricus) during hibernation. Acta Theriologica Sinica, 2011; 31: 387-395.
[[5]]
Johansson B W. The hibernator heart--nature’s model of resistance to ventricular fibrillation. Cardiovascular Research, 1996; 31: 826-832.
[[6]]
Wang S Q, Huang Y H, Liu K S, et al. Dependence of myocardial hypothermia tolerance on sources of activator calcium. Cryobiology, 1997; 35(3): 193-200.
[[7]]
Egorov Y V, Glukhov A V, Efimov I R, et al. Hypothermia-induced spatially discordant action potential duration alternans and arrhythmogenesis in nonhibernating versus hibernating mammals. Am J Physiol Heart Circ Physiol, 2012 ; 303(8): H1035-H1046.
[[8]]
Fedorov V V, Glukhov A V, Sudharshan S, et al. Electrophysiological mechanisms of antiarrhythmic protection during hypothermia in winter hibernating versus nonhibernating mammals. Heart Rhythm, 2008; 5(11): 1587-1596.
[[9]]
Wang S Q, Zhou Z Q. Medical significance of cardiovascular function in hibernating mammals. Clinical and Experimental Pharmacology & Physiology, 1999; 26(10): 837-839.
[[10]]
Frare C, Williams C T, Drew K L. Thermoregulation in hibernating mammals: The role of the “thyroid hormones system”. Mol Cell Endocrinol, 2021; 519(5): 111054.
[[11]]
Takahashi T M, Sunagawa G A, Soya S, et al. A discrete neuronal circuit induces a hibernation-like state in rodents. Nature, 2020; 583(7814): 109-114.
[[12]]
Hrvatin S, Sun S, Wilcox O F, et al. Neurons that regulate mouse torpor. Nature, 2020; 583: 115-121.
[[13]]
Blackstone E, Morrison M, Roth M B. H2S induces a suspended animation-like state in mice. Science, 2005; 308: 518.
[[14]]
Tupone D, Madden C J, Morrison S F. Central activation of the A1 adenosine receptor (A1AR) induces a hypothermic, torpor-like state in the rat. J Neurosci, 2013; 33: 14512-14525.
[[15]]
Jinka T R, Combs V M, Drew K L. Translating drug-induced hibernation to therapeutic hypothermia. ACS Chem Neurosci, 2015; 6: 899-904.
[[16]]
Nordrehaug J E. Sustained ventricular fibrillation in deep accidental hypothermia. British Medical Journal (Clinical Research Ed), 1982; 284: 867-868.
[[17]]
Physiology S O. The recovery of dogs from deep hypothermia. Acta Scientiarum Naturalium Universitatis Pekinensis, 1959; 5: 99-102.
[[18]]
Association A H. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 10.4: Hypothermia. Circulation, 2005;112(IV): 136-138.
[[19]]
Wang L. Mammalian hibernation: an escape from the cold. Berlin: Springer-Verlag, 1988.
[[20]]
Kamm K E, Zatzman M L, Jones A W, et al. Maintenance of ion concentration gradients in the cold in aorta from rat and ground squirrel. Am J Physiol, 1979; 237: C17-C22.
[[21]]
Wang S Q, Cao H M, ZHOU Z Q. Temperature dependence of the myocardial excitability of ground squirrel and rat. J Thermal Biol, 1997; 22: 195-199.
[[22]]
Zhao M J, Zhao Y B, Wei J H. Cold tolerance of the membrane potentials in cardiac cells of the ground squirrel citellus dauricus. Sheng Li Xue Bao, 1988; 40: 36-42.
[[23]]
Wang S, Zhou Z, Qian H. Temperature dependence of intracellular free calcium in cardiac myocytes from rat and ground squirrel measured by confocal microscopy. Sci China C Life Sci, 1999; 42: 293-299.
[[24]]
Wang S Q, Huang Y H, Zhou Z Q. Dependence of myocardial hypothermia resistance on sources of activator calcium. Cryobiol, 1997; 35: 193-200.
[[25]]
Li X C, Wei L, Zhang G Q, et al. Ca2+ cycling in heart cells from ground squirrels: adaptive strategies for intracellular Ca2+ homeostasis. PLoS One, 2011; 6:e24787.
[[26]]
Chien S, Oeltgen P R, Diana J N, et al. Two-day preservation of major organs with autoperfusion multiorgan preparation and hibernation induction trigger. A preliminary report. J Thorac Cardiovasc Surg, 1991; 102: 224-234.
[[27]]
Biorck G, Johansson B, Schmid H. Reactions of hedgehogs, hibernating and non-hibernating, to the inhalation of oxygen, carbon dioxide and nitrogen. Acta Physiol Scand, 1956; 37: 71-83.
[[28]]
D'Alecy L G, Lundy E F, Kluger M J, et al. Beta-hydroxybutyrate and response to hypoxia in the ground squirrel, Spermophilus tridecimlineatus. Comp Biochem Physiol B, 1990; 96: 189-193.
[[29]]
Drew K L, Wells M, McGee R, et al. Arctic ground squirrel neuronal progenitor cells resist oxygen and glucose deprivation-induced death. World J Biol Chem, 2016; 7: 168-177.
[[30]]
Singhal N S, Bai M, Lee E M, et al. Cytoprotection by a naturally occurring variant of ATP5G 1 in Arctic ground squirrel neural progenitor cells. Elife, 2020; 9.
[[31]]
Kerrigan C L, Stotland M A. Ischemia reperfusion injury: a review. Microsurgery, 1993; 14: 165-175.
[[32]]
Dirksen M T, Laarman G J, Simoons M L, et al. Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies. Cardiovasc Res, 2007; 74: 343-355.
[[33]]
Levitsky S. Protecting the myocardial cell during coronary revascularization. The William W. L. Glenn Lecture. Circulation, 2006; 114: I339-I343.
[[34]]
Gao T L, Huang Y Z, Jin W. The resistance to ischemia-reperfusion injury of the isolated heart from hibernator Citellus dauricus. Acta Scientiarum Naturalium Universitatis Pekinensis, 1996; 32: 527-533.
[[35]]
Ou J, Ball J M, Luan Y, et al. iPSCs from a Hibernator Provide a Platform for Studying Cold Adaptation and Its Potential Medical Applications. Cell, 2018; 173: 851-863, e816.
[[36]]
Eagles D A, Jacques L B, Taboada J, et al. Cardiac arrhythmias during arousal from hibernation in three species of rodents. Am J Physiol, 1988; 254: R102-R108.
[[37]]
Johansson B W. Ventricular repolarization and fibrillation threshold in hibernating species. Eur Heart J, 1985; 6 Suppl D: 53-62.
[[38]]
Martin S L. Mammalian hibernation: a naturally reversible model for insulin resistance in man? Diab Vasc Dis Res, 2008; 5: 76-81.
[[39]]
Stott N L, Marino J S. High fat rodent models of type 2 diabetes: from rodent to human. Nutrients, 2020; 12.
[[40]]
Arinell K, Sahdo B, Evans A L, et al. Brown bears (Ursus arctos) seem resistant to atherosclerosis despite highly elevated plasma lipids during hibernation and active state. Clin Transl Sci, 2012; 5: 269-272.
[[41]]
Naito H K, Gerrity R G. Unusual resistance of the ground squirrel to the development of dietary-induced hypercholesterolemia and atherosclerosis. Experimental and molecular pathology, 1979; 31: 452-467.
[[42]]
Ferris E, Gregg C. Parallel Accelerated Evolution in Distant Hibernators Reveals Candidate Cis Elements and Genetic Circuits Regulating Mammalian Obesity. Cell Rep, 2019; 29: 2608-2620, e2604.
[[43]]
Cotton C J, Harlow H J. Avoidance of skeletal muscle atrophy in spontaneous and facultative hibernators. Physiol Biochem Zool, 2010; 83: 551-560.
[[44]]
Lee K, Park J Y, Yoo W, et al. Overcoming muscle atrophy in a hibernating mammal despite prolonged disuse in dormancy: proteomic and molecular assessment. Journal of cellular biochemistry, 2008; 104: 642-656.
[[45]]
Wojda S J, McGee-Lawrence M E, Gridley R A, et al. Yellow-bellied marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation. Bone, 2012; 50: 182-188.
[[46]]
McGee-Lawrence M E, Carey H V, Donahue S W. Mammalian hibernation as a model of disuse osteoporosis: the effects of physical inactivity on bone metabolism, structure, and strength. Am J Physiol Regul Integr Comp Physiol, 2008; 295: R1999-R2014.
[[47]]
Gao Y F, Wang J, Wang H P, et al. Skeletal muscle is protected from disuse in hibernating dauria ground squirrels. Comp Biochem Physiol A Mol Integr Physiol, 2012; 161: 296-300.
[[48]]
Carey H V, Mangino M J, Southard J H. Changes in gut function during hibernation: implications for bowel transplantation and surgery. Gut, 2001; 49: 459-461.
PDF(244 KB)

Accesses

Citations

Detail

Sections
Recommended

/