Autonomic Control of Circulation During the Hibernating Cycle in Ground Squirrels

Lyman, C. P.; O'Brien, Regina C.

doi:10.21236/ad0410783

Cited by 11 publications

(15 citation statements)

References 10 publications

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“…One distinctive cardiovascular feature of natural torpor in mammals is the appearance of skipped beats, particularly during entry into torpor (Lyman and O'Brien 1963, Milsom, Zimmer et al 1999). Administration of atropine, a muscarinic antagonist, causes the disappearance of the skipped beats during a natural bout of torpor, suggesting that the skipped beats are mediated via the PNS (Milsom, Zimmer et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Central activation of the A1 adenosine receptor in fed mice recapitulates only some of the attributes of daily torpor

2017

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Mice enter bouts of daily torpor, drastically reducing metabolic rate, core body temperature (Tb), and heart rate (HR), in response to reduced caloric intake. Because central adenosine activation has been shown to induce a torpor-like state in the arctic ground squirrel, and blocking the adenosine-1 (A1) receptor prevents daily torpor, we hypothesized that central activation of the A1 adenosine receptors would induce a bout of natural torpor in mice. To test the hypothesis, mice were subjected to four different hypothermia bouts: natural torpor, forced hypothermia (FH), isoflurane-anesthesia, and an intracerebroventricular injection of the selective A1 receptor agonist N6cyclohexyladenosine (CHA). All conditions induced profound hypothermia. Tb fell more rapidly in the FH, isoflurane-anesthesia, and CHA conditions compared to torpor, while mice treated with CHA recovered at half the rate of torpid mice. FH, isoflurane-anesthesia, and CHA-treated mice exhibited a diminished drop in HR during entry into hypothermia as compared to torpor. Mice in all conditions except CHA shivered while recovering from hypothermia, and only FH mice shivered substantially while entering hypothermia. Circulating lactate during the hypothermic bouts was not significantly different between the CHA and torpor conditions, both of which had lower than baseline lactate levels. Arrhythmias were largely absent in the FH and isoflurane-anesthesia conditions, while skipped beats were observed in natural torpor and periodic extended (>1 sec) HR pauses in the CHA condition. Lastly, the hypothermic bouts showed distinct patterns of gene expression, with torpor characterized by elevated hepatic and cardiac Txnip expression and all other hypothermic states characterized by elevated c-Fos and Egr-1 expression. We conclude that CHA-induced hypothermia and natural torpor are largely different physiological states.

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Section: Discussionmentioning

confidence: 99%

Central activation of the A1 adenosine receptor in fed mice recapitulates only some of the attributes of daily torpor

2017

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“…The rewarming transition from torpor to euthermia is particularly intriguing, as skeletal muscle resumes contraction to contribute to rewarming in conjunction with perfusion restoration (37,38), intracellular pH changes (43), and apparent adjustments in fuel selection (23; but see also 33,47,60). Skeletal muscle must balance the retention of contractile functionality for arousals with energy conservation tactics required for the hibernation season.…”

Section: Winter Proteomementioning

confidence: 99%

“…We sampled early and late torpor states along with arousing and interbout aroused animals as well as those reentering torpor. As perfusion (37,38) and shivering amplitude lag in posterior regions (38), we expected early-and late-arousing animals, defined by abdominal T b , to represent markedly different physiology in hindlimb muscle.…”

mentioning

confidence: 99%

Skeletal muscle proteomics: carbohydrate metabolism oscillates with seasonal and torpor-arousal physiology of hibernation

Hindle¹,

Karimpour-Fard

Epperson³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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The physiology of small mammalian hibernators shifts profoundly over a year, from summer homeothermy to winter heterothermy. Torpor-arousal cycles define high-amplitude tissue activity fluctuations in winter, particularly for skeletal muscle, which contributes to the energetically demanding rewarming process via shivering. To better understand the biochemistry underlying summer-winter and torpor-arousal transitions, we applied two-dimensional gel electrophoresis coupled with liquid chromatography/mass spectrometry/mas spectrometry to the soluble proteins from hindlimb muscle of 13-lined ground squirrels (Ictidomys tridecemlineatus) in two summer and six winter states. Two hundred sixteen protein spots differed by sampled state. Significantly, intrawinter protein adjustment was a minor component of the dataset despite large discrepancies in muscle activity level among winter states; rather, the bulk of differences (127/138 unequivocally identified proteins spots) occurred between summer and winter. We did not detect any proteomic signatures of skeletal muscle atrophy in this hibernator nor any differential seasonal regulation of protein metabolism. Instead, adjustments to metabolic substrate preferences dominated the detected proteomic differences. Pathways of carbohydrate metabolism (glycolysis and gluconeogenesis) were summer enriched, whereas the winter proteome was enriched for fatty acid β-oxidation. Nevertheless, our data suggest that some reliance on carbohydrate reserves is maintained during winter. Phosphoglucomutase (PGM1), which reversibly prepares glucose subunits for either glycolysis or glycogenesis, showed apparent winter state-specific phosphorylation. PGM1 was phosphorylated during rewarming and dephosphorylated by interbout arousal, implying that glucose supplements lipid fuels during rewarming. This, along with winter elevation of TCA cycle enzymes, suggests that hindlimb muscles are primed for rapid energy production and that carbohydrates are an important fuel for shivering thermogenesis.

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“…An opposing theory that has gained more widespread acceptance is that parasympathetic modulation disappears during prolonged torpor (Lyman 1982). Parasympathetic nervous system activity is suggested to wane as temperature falls because it is thought that low T b ’s normally associated with states, such as deep torpor are incompatible with parasympathetic nervous system function (Lyman and O’Brien 1963; Lyman 1982; Harris and Milsom 1995). Both theories have drawn evidence from studies of heart rate during torpor, and this has been the topic of a detailed review (Milsom et al.…”

Section: Theories Of Autonomic Nervous System Control Of Torpormentioning

confidence: 99%

Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance

Drew

Buck

Barnes

et al. 2007

Journal of Neurochemistry

163

147

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Torpor during hibernation defines the nadir of mammalian metabolism where whole animal rates of metabolism are decreased to as low as 2% of basal metabolic rate. This capacity to decrease profoundly the metabolic demand of organs and tissues has the potential to translate into novel therapies for the treatment of ischemia associated with stroke, cardiac arrest or trauma where delivery of oxygen and nutrients fails to meet demand. If metabolic demand could be arrested in a regulated way, cell and tissue injury could be attenuated. Metabolic suppression achieved during hibernation is regulated, in part, by the central nervous system through indirect and possibly direct means. In this study, we review recent evidence for mechanisms of central nervous system control of torpor in hibernating rodents including evidence of a permissive, hibernation protein complex, a role for A1 adenosine receptors, mu opiate receptors, glutamate and thyrotropin-releasing hormone. Central sites for regulation of torpor include the hippocampus, hypothalamus and nuclei of the autonomic nervous system. In addition, we discuss evidence that hibernation phenotypes can be translated to non-hibernating species by H 2 S and 3-iodothyronamine with the caveat that the hypothermia, bradycardia, and metabolic suppression induced by these compounds may or may not be identical to mechanisms employed in true hibernation. Keywords metabolic arrest; metabolic suppression; suspended animationHibernating animals display a variety of adaptations that protect the central nervous system from metabolic challenges and trauma that are injurious in non-hibernating species. These adaptations include profound decreases in brain and body temperature (T b ) and immune function, enhanced antioxidant defenses, and metabolic suppression Zhou et al. 2001; Ross et al. 2006). Metabolic suppression, a regulated and reversible reduction in cellular and tissue need for oxygen and nutrients, matches metabolic demand with supply and is one of the most novel yet least well-understood neuroprotective aspects of hibernation. Knowledge of mechanisms used by hibernating animals to decrease metabolic demand to as low as 2% of basal metabolic rate or 0.01 mL O 2 /g/h

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Autonomic Control of Circulation During the Hibernating Cycle in Ground Squirrels

Cited by 11 publications

References 10 publications

Central activation of the A1 adenosine receptor in fed mice recapitulates only some of the attributes of daily torpor

Central activation of the A1 adenosine receptor in fed mice recapitulates only some of the attributes of daily torpor

Skeletal muscle proteomics: carbohydrate metabolism oscillates with seasonal and torpor-arousal physiology of hibernation

Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance

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