Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Abstract

Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as -2.9 degrees C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0 degrees C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.

Upregulation of intracellular antioxidant enzymes in brain and heart during estivation in the African lungfish Protopterus dolloi

“…Several authors (e.g. Hermes-Lima and Zenteno-Savín 2002; Carey et al 2003) have suggested that this cellular resistance is mediated in part by the upregulation of antioxidant enzymes, possibly to ameliorate macromolecular damage from ROS production during arousal from torpor. We tested the hypothesis that the African lungWsh P. dolloi adaptively enhances antioxidant capacity during estivation.…”

“…Hermes-Lima and Zenteno-Savín 2002; Carey et al 2003) have suggested that upregulation of intracellular antioxidant enzymes during estivation and hibernation protects against stress-related cellular injury. Indeed, there is some evidence for this in estivating pulmonate land snails (Hermes-Lima and Storey 1995;RamosVasconcelos and Hermes-Lima 2003).…”

Expression profile of Bag 1 in the postmortem brain

“…This hypothetical scenario is reasonable at a storage temperature of 24 °C, with Bag 1 suppressing cell death. At a storage temperature of 4 °C, however, Bag 1 appears to undergo a profound metabolic depression reminiscent of a torpor state for reducing energy costs (Carey et al, 2003). Regardless, our data provide ex vivo evidence for a crucial role of temperature in Bag 1 kinetics.…”

A simple molecular mathematical model of mammalian hibernation

“…Many genes are differentially regulated between summer and winter in hibernators, and many proteins undergo post-translational modifications (Carey et al, 2003;Lee et al, 2006). These differentially expressed genes include α 2 -macroglobulin (Srere et al, 1995), the H3 histamine receptor (Sallmen et al, 2003), TBG (thyroxine binding globulin) (Epperson and Martin, 2002), and the 'early-intermediate' genes such as c-fos and c-jun (O'Hara et al, 1999).…”

“…Despite the fact that hibernators are widespread among the Mammalia (Carey et al, 2003), the study of mammalian hibernation in the past has not benefited from the availability of defined mutants, stock centers, or sequenced genomes. Low coverage genome sequencing has only recently begun on three distantly related hibernating mammals: the little brown bat (Myotis lucifugus), European hedgehog (Erinaceus europaeus), and thirteen-lined ground squirrel (Spermophilus tridecemlineatus).…”