Mammalian hibernation: a unique model for medical research

Xin Xing; Shiqiang Wang

doi:10.2478/fzm-2021-0008

Mammalian hibernation: a unique model for medical research

doi: 10.2478/fzm-2021-0008

Xin Xing¹,
Shiqiang Wang^{2, 3
, ,}

1.
College of Life Science, Shenyang Normal University, Shenyang 110034, China
2.
State Key Laboratory of Membrane Biology, College of Life Science, Peking University, Beijing 100871, China
3.
Chinese Institute for Brain Research, Beijing 102206, China

More Information

Corresponding author: Shiqiang Wang, E-mail: wsq@pku.edu.cn

摘要

Abstract:
Hibernation is an adaptive behavior for some small animals to survive cold winter. Hibernating mammals usually down-regulate their body temperature from ~37℃ 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.
- hibernation /
- deep hypothermia /
- hypoxia /
- osteoporosis /
- muscle atrophy /
- arrhythmia /
- ischemia-reperfusion

HTML全文

参考文献(48)

[1]	Andrews M T. Advances in molecular biology of hibernation in mammals. Bioessays, 2007; 29(5): 431-440. doi: 10.1002/bies.20560
[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. doi: 10.1152/physrev.00008.2003
[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. http://en.cnki.com.cn/Article_en/CJFDTOTAL-SLXX201104011.htm
[5]	Johansson B W. The hibernator heart--nature's model of resistance to ventricular fibrillation. Cardiovascular Research, 1996; 31: 826-832. http://europepmc.org/abstract/MED/8763414
[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. doi: 10.1006/cryo.1997.2040
[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. doi: 10.1152/ajpheart.00786.2011
[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. doi: 10.1016/j.hrthm.2008.08.030
[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. http://www.ncbi.nlm.nih.gov/pubmed/10549417
[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. http://www.sciencedirect.com/science/article/pii/S0303720720303567
[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. doi: 10.1038/s41586-020-2163-6
[12]	Hrvatin S, Sun S, Wilcox O F, et al. Neurons that regulate mouse torpor. Nature, 2020; 583: 115-121. doi: 10.1038/s41586-020-2387-5
[13]	Blackstone E, Morrison M, Roth M B. H2S induces a suspended animation-like state in mice. Science, 2005; 308: 518. doi: 10.1126/science.1108581
[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. doi: 10.1523/JNEUROSCI.1980-13.2013
[15]	Jinka T R, Combs V M, Drew K L. Translating drug-induced hibernation to therapeutic hypothermia. ACS Chem Neurosci, 2015; 6: 899-904. doi: 10.1021/acschemneuro.5b00056
[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. doi: 10.1152/ajpcell.1979.237.1.C17
[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. doi: 10.1016/S0306-4565(97)00010-7
[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. http://www.ncbi.nlm.nih.gov/pubmed/3388062
[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. doi: 10.1007/BF03183606
[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. doi: 10.1006/cryo.1997.2040
[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. doi: 10.1371/journal.pone.0024787
[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. doi: 10.1016/S0022-5223(19)36555-9
[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. doi: 10.1111/j.1748-1716.1956.tb01343.x
[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. doi: 10.1016/0305-0491(90)90361-V
[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. doi: 10.4331/wjbc.v7.i1.168
[30]	Singhal N S, Bai M, Lee E M, et al. Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells. Elife, 2020; 9. http://www.ncbi.nlm.nih.gov/pubmed/33050999
[31]	Kerrigan C L, Stotland M A. Ischemia reperfusion injury: a review. Microsurgery, 1993; 14: 165-175. doi: 10.1002/micr.1920140307
[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. doi: 10.1016/j.cardiores.2007.01.014
[33]	Levitsky S. Protecting the myocardial cell during coronary revascularization. The William W. L. Glenn Lecture. Circulation, 2006; 114: I339-I343. http://www.ncbi.nlm.nih.gov/pubmed/16820597
[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. http://europepmc.org/abstract/cba/296798
[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. doi: 10.1016/j.cell.2018.03.010
[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. http://www.onacademic.com/detail/journal_1000038746440310_b6a7.html
[38]	Martin S L. Mammalian hibernation: a naturally reversible model for insulin resistance in man? Diab Vasc Dis Res, 2008; 5: 76-81. doi: 10.3132/dvdr.2008.013
[39]	Stott N L, Marino J S. High fat rodent models of type 2 diabetes: from rodent to human. Nutrients, 2020; 12. http://www.researchgate.net/publication/346554101_High_Fat_Rodent_Models_of_Type_2_Diabetes_From_Rodent_to_Human
[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. doi: 10.1111/j.1752-8062.2011.00370.x
[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. doi: 10.1016/0014-4800(79)90044-3
[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. doi: 10.1016/j.celrep.2019.10.102
[43]	Cotton C J, Harlow H J. Avoidance of skeletal muscle atrophy in spontaneous and facultative hibernators. Physiol Biochem Zool, 2010; 83: 551-560. doi: 10.1086/650471
[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. doi: 10.1002/jcb.21653
[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. doi: 10.1016/j.bone.2011.10.013
[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. doi: 10.1152/ajpregu.90648.2008
[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. doi: 10.1016/j.cbpa.2011.11.009
[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. doi: 10.1136/gut.49.4.459