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Abstract

Grant Number:	1DP1OD000895-01
Project Title:	NIH Director's Pioneer Award

PI Information:	Name	Email	Title
	LEE, CHENG C.	cheng.c.lee@uth.tmc.edu	ASSOCIATE PROFESSOR

Abstract: During hibernation, certain mammals can undergo a physiological state analogous to reversible suspended animation, with severe hypothermia and a core body temperature (CBT) close to 0 degrees C. In non-hibernators including the human, this degree of hypothermia is fatal. It is well established that cells under hypoxia survive longer in hypothermic conditions due to slowing of metabolism, a feature with many clinical applications. Due to the risk of organ failure, clinical application of hypothermia is limited to a CBT of 32-34 degrees C. Even at this temperature, the beneficial effect of controlled hypothermia is significant. The laboratory mouse is a non-hibernator but under caloric restriction it can undergo torpor (hibernating-like) behavior with a CBT of 31 degrees C or below. Primates such as Malagasy lemurs can undergo torpor, suggesting that the basic mechanism for such behavior may be preserved in humans. We have recently identified endogenous 5?-adenosine monophosphate (5?-AMP) as a mediator of torpor behavior in mice. Our studies revealed that torpor behavior is linked to the regulation of blood glucose by 5?-AMP, an important allosteric regulator of several rate-limiting enzymes involved in glucose homeostasis. Our finding raised the possibility that non-hibernators can also achieve a state of suspended animation observed only in hibernating mammals. Using the physiological variables, 5?- AMP, environmental temperature and glucose, we can induce, sustain and rescue mice in suspended animation. Shivering, a sign of thermo-regulatory defense, is blocked by 5?-AMP, allowing rapid cooling of CBT to 17 degrees C or below, causing the animal to enter suspended animation. Recovery from a suspended animation state of up to 10 hours is spontaneous but was enhanced by glucose. Our goal is to bring this technology into two areas. 1) To explore the physiological limits of suspended animation in non-hibernating mammals. 2) To extend findings from the laboratory mouse to other non-hibernating mammals along the evolutionary chain.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
adenosine monophosphate, body temperature, hibernation, induced hypothermia, technology /technique development
environment, evolution, glucose metabolism, molecular dynamics, temperature, thermostability
NIH Roadmap Initiative tag, laboratory mouse

Institution:	UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
	BOX 20036
	HOUSTON, TX 77225
Fiscal Year:	2006
Department:	BIOCHEM AND MOLECULAR BIOLOGY
Project Start:	28-SEP-2006
Project End:	31-JUL-2011
ICD:	OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
IRG:	ZGM1

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