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Frontiers in Physiology 2023Hibernating mammals have developed many physiological adaptations to accommodate their decreased metabolism, body temperature, heart rate and prolonged immobility... (Review)
Review
Hibernating mammals have developed many physiological adaptations to accommodate their decreased metabolism, body temperature, heart rate and prolonged immobility without suffering organ injury. During hibernation, the animals must suppress blood clotting to survive prolonged periods of immobility and decreased blood flow that could otherwise lead to the formation of potentially lethal clots. Conversely, upon arousal hibernators must be able to quickly restore normal clotting activity to avoid bleeding. Studies in multiple species of hibernating mammals have shown reversible decreases in circulating platelets, cells involved in hemostasis, as well as in protein coagulation factors during torpor. Hibernator platelets themselves also have adaptations that allow them to survive in the cold, while those from non-hibernating mammals undergo lesions during cold exposure that lead to their rapid clearance from circulation when re-transfused. While platelets lack a nucleus with DNA, they contain RNA and other organelles including mitochondria, in which metabolic adaptations may play a role in hibernator's platelet resistance to cold induced lesions. Finally, the breakdown of clots, fibrinolysis, is accelerated during torpor. Collectively, these reversible physiological and metabolic adaptations allow hibernating mammals to survive low blood flow, low body temperature, and immobility without the formation of clots during torpor, yet have normal hemostasis when not hibernating. In this review we summarize blood clotting changes and the underlying mechanisms in multiple species of hibernating mammals. We also discuss possible medical applications to improve cold preservation of platelets and antithrombotic therapy.
PubMed: 37435313
DOI: 10.3389/fphys.2023.1207003 -
JACC. Clinical Electrophysiology Nov 2021
Topics: Heart Rate; Hibernation; Humans; Sinoatrial Node
PubMed: 34794663
DOI: 10.1016/j.jacep.2021.04.006 -
Comparative Biochemistry and... Mar 2021For hibernating mammals, the transition from summer active to winter hibernation seasons come with significant remodeling at cellular, organ and whole organism levels.... (Review)
Review
For hibernating mammals, the transition from summer active to winter hibernation seasons come with significant remodeling at cellular, organ and whole organism levels. This review summarizes and synthesizes what is known about hibernation-related remodeling in the gastrointestinal tract of the thirteen-lined ground squirrel, including intestinal and hepatic physiology and the gut microbiota. Hibernation alters intestinal epithelial, immune and cell survival pathways in ways that point to a protective phenotype in the face of prolonged fasting and major fluctuations in nutrient and oxygen delivery during torpor-arousal cycles. The prolonged fasting associated with hibernation alters lipid metabolism and systemic cholesterol dynamics, with both the gut and liver participating in these changes. Fasting also affects the gut microbiota, altering the abundance, composition and diversity of gut microbes and impacting the metabolites they produce in ways that may influence hibernation-related traits in the host. Finally, interventional studies have demonstrated that the hibernation phenotype confers resistance to experimental ischemia-reperfusion injury in both gut and liver, suggesting potential therapeutic roadmaps. We propose that the plasticity inherent to hibernation biology may contribute to this stress tolerance, and in the spirit of August Krogh, makes hibernators particularly valuable for study to identify solutions to certain problems.
Topics: Animals; Cholesterol; Fatty Acids, Nonesterified; Gastrointestinal Microbiome; Gastrointestinal Tract; Hibernation; Lipoproteins; Liver; Sciuridae; Seasons
PubMed: 33348019
DOI: 10.1016/j.cbpa.2020.110875 -
Current Biology : CB Mar 2013Hibernation (multiday torpor) and daily torpor in heterothermic mammals and birds are characterized by pronounced temporal reductions in body temperature, energy... (Review)
Review
Hibernation (multiday torpor) and daily torpor in heterothermic mammals and birds are characterized by pronounced temporal reductions in body temperature, energy expenditure, water loss, and other physiological functions and are the most effective means for energy conservation available to endotherms. Hibernators express multiday torpor predominately throughout winter, which substantially enhances winter survival. In contrast, daily heterotherms use daily torpor lasting for several hours during the rest phase. Although torpor is still widely considered to be a specific adaptation of cold-climate species, as we will see in this primer, it is used by many diverse species from all climate zones, including the tropics. While energy conservation during adverse conditions is an important function of torpor, it is also employed to permit energy-demanding processes such as reproduction and growth, especially when food supply is limited. Even migrating birds enter torpor to conserve energy for the next stage of migration. Although many heterothermic species will be challenged by anthropogenic influences such as habitat destruction, introduced species, novel pathogens and specifically global warming, not all are likely to be affected in the same way. In fact, as argued here, it is likely that opportunistic heterotherms may be better equipped to deal with these challenges than homeotherms because heterotherms have highly flexible energy requirements, can limit foraging and reduce the risk of predation, and often are also long-lived. In contrast, strongly seasonal hibernators, especially those restricted to mountain tops, and those that have to deal with new diseases that are difficult to combat at low body temperatures, are likely to be adversely affected.
Topics: Animals; Circadian Rhythm; Climate Change; Hibernation; Seasons
PubMed: 23473557
DOI: 10.1016/j.cub.2013.01.062 -
Current Opinion in Microbiology Aug 2021Hibernation, a period where bats have suppressed immunity and low body temperatures, provides the psychrophilic fungus Pseudogymnoascus destructans the opportunity to... (Review)
Review
Hibernation, a period where bats have suppressed immunity and low body temperatures, provides the psychrophilic fungus Pseudogymnoascus destructans the opportunity to colonise bat skin, leading to severe disease in susceptible species. Innate immunity, which requires less energy and may remain more active during torpor, can control infections with local inflammation in some bat species that are resistant to infection. If infection is not controlled before emergence from hibernation, ineffective adaptive immune mechanisms are activated, including incomplete Th1, ineffective Th2, and variable Th17 responses. The Th17 and neutrophil responses, normally beneficial antifungal mechanisms, appear to be sources of immunopathology for susceptible bat species, because they are hyperactivated after return to homeothermy. Non-susceptible species show both well-balanced and suppressed immune responses both during and after hibernation.
Topics: Animals; Antifungal Agents; Ascomycota; Chiroptera; Hibernation
PubMed: 34098511
DOI: 10.1016/j.mib.2021.05.002 -
Physiology (Bethesda, Md.) Sep 2022Hibernators rapidly and reversibly suppress mitochondrial respiration and whole animal metabolism. Posttranslational modifications likely regulate these mitochondrial... (Review)
Review
Hibernators rapidly and reversibly suppress mitochondrial respiration and whole animal metabolism. Posttranslational modifications likely regulate these mitochondrial changes, which may help conserve energy in winter. These modifications are affected by reactive oxygen species (ROS), so suppressing mitochondrial ROS production may also be important for hibernators, just as it is important for surviving ischemia-reperfusion injury.
Topics: Animals; Energy Metabolism; Hibernation; Mitochondria; Reactive Oxygen Species; Sciuridae
PubMed: 35658625
DOI: 10.1152/physiol.00006.2022 -
PloS One 2021Hibernating mammals exhibit unique metabolic and physiological phenotypes that have potential applications in medicine or spaceflight, yet our understanding of the...
Hibernating mammals exhibit unique metabolic and physiological phenotypes that have potential applications in medicine or spaceflight, yet our understanding of the genetic basis and molecular mechanisms of hibernation is limited. The meadow jumping mouse, a small North American hibernator, exhibits traits-including a short generation time-that would facilitate genetic approaches to hibernation research. Here we report the collection, captive breeding, and laboratory hibernation of meadow jumping mice. Captive breeders in our colony produced a statistically significant excess of male offspring and a large number of all-male and all-female litters. We confirmed that short photoperiod induced pre-hibernation fattening, and cold ambient temperature facilitated entry into hibernation. During pre-hibernation fattening, food consumption exhibited non-linear dependence on both body mass and temperature, such that food consumption was greatest in the heaviest animals at the coldest temperatures. Meadow jumping mice exhibited a strong circadian rhythm of nightly activity that was disrupted during the hibernation interval. We conclude that it is possible to study hibernation phenotypes using captive-bred meadow jumping mice in a laboratory setting.
Topics: Animals; Breeding; Circadian Rhythm; Feeding Behavior; Female; Hibernation; Locomotion; Male; Mice; Phenotype; Photoperiod; Species Specificity; Temperature; Weight Gain
PubMed: 33970917
DOI: 10.1371/journal.pone.0240706 -
Scientific Reports Mar 2021In nature, photoperiod signals environmental seasonality and is a strong selective "zeitgeber" that synchronizes biological rhythms. For animals facing seasonal...
In nature, photoperiod signals environmental seasonality and is a strong selective "zeitgeber" that synchronizes biological rhythms. For animals facing seasonal environmental challenges and energetic bottlenecks, daily torpor and hibernation are two metabolic strategies that can save energy. In the wild, the dwarf lemurs of Madagascar are obligate hibernators, hibernating between 3 and 7 months a year. In captivity, however, dwarf lemurs generally express torpor for periods far shorter than the hibernation season in Madagascar. We investigated whether fat-tailed dwarf lemurs (Cheirogaleus medius) housed at the Duke Lemur Center (DLC) could hibernate, by subjecting 8 individuals to husbandry conditions more in accord with those in Madagascar, including alternating photoperiods, low ambient temperatures, and food restriction. All dwarf lemurs displayed daily and multiday torpor bouts, including bouts lasting ~ 11 days. Ambient temperature was the greatest predictor of torpor bout duration, and food ingestion and night length also played a role. Unlike their wild counterparts, who rarely leave their hibernacula and do not feed during hibernation, DLC dwarf lemurs sporadically moved and ate. While demonstrating that captive dwarf lemurs are physiologically capable of hibernation, we argue that facilitating their hibernation serves both husbandry and research goals: first, it enables lemurs to express the biphasic phenotypes (fattening and fat depletion) that are characteristic of their wild conspecifics; second, by "renaturalizing" dwarf lemurs in captivity, they will emerge a better model for understanding both metabolic extremes in primates generally and metabolic disorders in humans specifically.
Topics: Animals; Cheirogaleidae; Feeding Behavior; Female; Hibernation; Linear Models; Male; North Carolina; Photoperiod; Temperature; Time Factors; Torpor; Weight Loss
PubMed: 33707506
DOI: 10.1038/s41598-021-84727-3 -
Cells Dec 2023Alzheimer's disease (AD) is the most common cause of dementia worldwide and yet remains without effective therapy. Amongst the many proposed causes of AD, the... (Review)
Review
Alzheimer's disease (AD) is the most common cause of dementia worldwide and yet remains without effective therapy. Amongst the many proposed causes of AD, the mitochondrial cascade hypothesis is gaining attention. Accumulating evidence shows that mitochondrial dysfunction is a driving force behind synaptic dysfunction and cognitive decline in AD patients. However, therapies targeting the mitochondria in AD have proven unsuccessful so far, and out-of-the-box options, such as hibernation-derived mitochondrial mechanisms, may provide valuable new insights. Hibernators uniquely and rapidly alternate between suppression and re-activation of the mitochondria while maintaining a sufficient energy supply and without acquiring ROS damage. Here, we briefly give an overview of mitochondrial dysfunction in AD, how it affects synaptic function, and why mitochondrial targeting in AD has remained unsuccessful so far. We then discuss mitochondria in hibernation and daily torpor in mice, covering current advancements in hibernation-derived mitochondrial targeting strategies. We conclude with new ideas on how hibernation-derived dual mitochondrial targeting of both the ATP and ROS pathways may boost mitochondrial health and induce local synaptic protein translation to increase synaptic function and plasticity. Further exploration of these mechanisms may provide more effective treatment options for AD in the future.
Topics: Humans; Animals; Mice; Hibernation; Alzheimer Disease; Reactive Oxygen Species; Mitochondria; Mitochondrial Diseases
PubMed: 38201215
DOI: 10.3390/cells13010012 -
Scientific Reports Aug 2018Hibernation is characterized by reduced metabolism and body temperature during torpor bouts. Energy reserves available during winter play an important role for...
Hibernation is characterized by reduced metabolism and body temperature during torpor bouts. Energy reserves available during winter play an important role for hibernation and some species respond to high energy reserves with reduced torpor expression. Common hamsters are food-storing hibernators and females hibernate for shorter periods than males, probably related to larger food stores. In this study, we provided free-ranging common hamsters with sunflower seeds shortly before winter and recorded body temperature using subcutaneously implanted data loggers. We compared hibernation patterns and body mass changes between individuals with and without food supplements and analysed reproductive onset in females. Supplemented males delayed hibernation onset, hibernated for much shorter periods, and emerged in spring with higher body mass than unsupplemented ones. Additional food did not affect hibernation performance in females, but supplemented females emerged earlier and preceded those without food supplements in reproductive onset. Thus, males and females differently responded to food supplementation: access to energy-rich food stores enabled males to shorten the hibernation period and emerge in better body condition, probably enhancing mating opportunities and reproductive success. Females did not alter hibernation patterns, but started to reproduce earlier than unsupplemented individuals, enabling reproductive benefits by an extended breeding period.
Topics: Analysis of Variance; Animals; Body Temperature; Body Weight; Cricetinae; Dietary Supplements; Female; Hibernation; Male; Reproduction; Sex Characteristics; Time Factors; Torpor
PubMed: 30166598
DOI: 10.1038/s41598-018-31520-4