Resistance to Systemic Inflammation and Multi Organ Damage after Global Ischemia/Reperfusion in the Arctic Ground Squirrel

Bogren, Lori K.; Olson, Jasmine M.; Carpluk, JoAnna; Moore, Jeanette; Drew, Kelly L.

doi:10.1371/journal.pone.0094225

Cited by 45 publications

(47 citation statements)

References 43 publications

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“…How mammalian hibernators are able to adapt to rapidly fluctuating oxygen levels without incurring oxidative damage, and how they avoid reperfusion injury in the brain and other sensitive tissues, is not well understood. Multiple studies have shown that hibernators display resistance to ischemia/reperfusion injury and, during torpor, increase expression of molecules that help regulate oxidative stress, such as superoxide dismutase 1 and 2, catalase, and glutathione peroxidase (2,(43)(44)(45)(46). Interestingly, uncoupling proteins have been linked to reduction of reactive oxygen species formation (47).…”

Section: Discussionmentioning

confidence: 99%

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Laursen

Mastrotto

Pesta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as −2.9°C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. We report, using differential transcriptomics alongside immunohistologic and biochemical analyses, that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) express mitochondrial uncoupling protein 1 (UCP1). The expression changes seasonally, with higher expression during hibernation compared with the summer active state. Functional and pharmacologic analyses show that squirrel UCP1 acts as the typical thermogenic protein in vitro. Accordingly, we found that mitochondria isolated from torpid squirrel brain show a high level of palmitate-induced uncoupling. Furthermore, torpid squirrels during the hibernation season keep their brain temperature significantly elevated above ambient temperature and that of the rest of the body, including brown adipose tissue. Together, our findings suggest that UCP1 contributes to local thermogenesis in the squirrel brain, and thus supports nervous tissue function at low body temperature during hibernation.T hirteen-lined ground squirrels (Ictidomys tridecemlineatus) are obligatory hibernating mammals. They are found across a wide range of latitudes, from southern Canada to the Gulf of Mexico. In northern habitats with long winters and limited food resources, ground squirrels breed only once a year, in late spring, and then hibernate in underground burrows from October to April. Hibernation consists of cycling between bouts of torpor and brief interbout arousal periods, each usually lasting less than 24 h (1, 2).During the long hibernation season, torpid animals undergo dramatic perturbations, including reduction in heart, respiratory, and overall metabolic rates, as well as decreases in core body temperature from 37°C to just above ambient temperature (often as low as 1-5°C) (2). Despite such a depressed physiologic phenotype, torpid animals remain sensitive to their environment (3). For example, during extreme winters, when ambient burrow temperatures reach the freezing point of water, most hibernating mammals increase metabolic activity and warm up as a safety precaution to prevent freezing (4). Similarly, arousal can be triggered by sound, touch, or a sudden increase in ambient temperature (3, 5). Thus, hibernating animals maintain activity in their peripheral and central nervous systems. Indeed, physiologic experiments conducted on nerve fibers isolated from torpid hamsters and squirrels demonstrated the ability to generate action potentials at temperatures prohibitively low for their nonhibernating relatives (i.e., rats, mice) (6-8).Deeply hibernating animals can keep their brain temperatures elevated above ambient by seve...

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Section: Discussionmentioning

confidence: 99%

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Laursen

Mastrotto

Pesta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…On the other hand, livers removed from summer ground squirrels and stored cold for up to 72 h retain viability and function better than rats, and this retention of performance actually improves in the hibernation season (178). Accordingly, cardiac arrest has virtually no effect on arctic ground squirrel liver, but causes considerable damage in rats (25). Because mammalian brain is inherently susceptible to interruptions of blood flow and O 2 supply, hibernator brains have been studied extensively.…”

Section: Are Hibernators Better At Withstanding Hypoxia/ischemia?mentioning

confidence: 99%

“…In rats, cardiac arrest damages a large proportion of CA1 hippocampal neurons, but virtually no damage is seen in euthermic arctic ground squirrels (74). Tissue ischemia resistance may also translate to higher levels of organization, as arctic ground squirrels survive extreme blood loss better than rats (25).…”

Section: Are Hibernators Better At Withstanding Hypoxia/ischemia?mentioning

confidence: 99%

Metabolic Flexibility: Hibernation, Torpor, and Estivation

Staples

2016

Comprehensive Physiology

136

116

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Many environmental conditions can constrain the ability of animals to obtain sufficient food energy, or transform that food energy into useful chemical forms. To survive extended periods under such conditions animals must suppress metabolic rate to conserve energy, water, or oxygen. Amongst small endotherms, this metabolic suppression is accompanied by and, in some cases, facilitated by a decrease in core body temperature-hibernation or daily torpor-though significant metabolic suppression can be achieved even with only modest cooling. Within some ectotherms, winter metabolic suppression exceeds the passive effects of cooling. During dry seasons, estivating ectotherms can reduce metabolism without changes in body temperature, conserving energy reserves, and reducing gas exchange and its inevitable loss of water vapor. This overview explores the similarities and differences of metabolic suppression among these states within adult animals (excluding developmental diapause), and integrates levels of organization from the whole animal to the genome, where possible. Several similarities among these states are highlighted, including patterns and regulation of metabolic balance, fuel use, and mitochondrial metabolism. Differences among models are also apparent, particularly in whether the metabolic suppression is intrinsic to the tissue or depends on the whole-animal response. While in these hypometabolic states, tissues from many animals are tolerant of hypoxia/anoxia, ischemia/reperfusion, and disuse. These natural models may, therefore, serve as valuable and instructive models for biomedical research.

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“…Many animals such as birds and mammals drastically reduce energy expenditure during times of cold exposure, food shortage, or drought, by temporarily abandoning optimal body temperature by a process called torpor (seasonal torpor in case of hibernation, daily torpor at night). A state of torpor might represent a cold ischemia condition, which could be followed by reperfusion when temperature and metabolism are restored [76]. In this respect, necroptosis has been shown to contribute to damage induced by ischemia-reperfusion injury [77].…”

Section: Rhim-mediated Interactions Evolved To Activate Necroptosis Imentioning

confidence: 99%

An evolutionary perspective on the necroptotic pathway

Dondelinger

Hulpiau

Saeys

et al. 2016

Trends in Cell Biology

132

113

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Resistance to Systemic Inflammation and Multi Organ Damage after Global Ischemia/Reperfusion in the Arctic Ground Squirrel

Cited by 45 publications

References 43 publications

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

Metabolic Flexibility: Hibernation, Torpor, and Estivation

An evolutionary perspective on the necroptotic pathway

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