Hibernation Induced in Ground Squirrels by Blood Transfusion

Dawe, Albert R.; Spurrier, Wilma A.

doi:10.1126/science.163.3864.298

Cited by 106 publications

(28 citation statements)

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“…This is a difficult because no practical predictive biochemical marker of the onset of hibernation has been demonstrated. Initial transfusion experiments demonstrated the existence of a blood-born "hibernation inducing trigger (HIT)" with seasonal profile compatible for a role in hibernation (Dawe and Spurrier, 1969;Oeltgen et al, 1978).…”

Section: Molecular Prospective Of Hibernationmentioning

confidence: 99%

Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

Hashimoto

Gao

Kikuchi-Utsumi

et al. 2002

Journal of Thermal Biology

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Section: Molecular Prospective Of Hibernationmentioning

confidence: 99%

Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

Hashimoto

Gao

Kikuchi-Utsumi

et al. 2002

Journal of Thermal Biology

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“…A mixture of 5% C02/95% air was pumped (=3 ml/min) through the vials while they were stirred at 370C. The outflow gas bubbled through 4 [1][2][3][4][5][6][7][8][9][10] took place at about the same rate as that observed after a single addition (Fig. 3 A and B).…”

mentioning

confidence: 72%

“…Rate of dThd uptake was determined by preincubating 1 (17). Fluorography was performed as described (18).…”

mentioning

confidence: 99%

Extracts from the brains of hibernating and alert ground squirrels: effects on cells in culture.

Amorese¹,

Swan²,

Bamburg³

1982

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

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Aqueous extracts were prepared from pulverized, acetone-dehydrated brains of hibernating and alert ground squirrels. Addition ofthese extracts to Chinese hamster ovary cells in suspension culture resulted in a decrease in the amount of [3H]thymidine incorporated into acid-precipitable material without affecting the transport or phosphorylation of the nucleoside. The inhibition was time-and dose-dependent and full recovery occurred about 2 hr after exposure ofthe cells to the active extract.The active factor is readily oxidized during storage at -700C but full activity can be restored by treatment with 2-mercaptoethanol. The peptide nature of the active material is indicated by its susceptibility to proteases and by loss of activity after alkylation. Fasted or cold-acclimated rats also develop increased levels of active substance in their brains; however, brains of hibernating squirrels contain 10-to 50-fold more of the active substance than brains from either alert squirrels or rats. A time-dependent increase in activity ofextracts from hibernating brain incubated with a homogenate from alert brain suggests that the peptide is activated or generated in the mixture.Attempts have been made to isolate and identify factors that induce or regulate the hibernating state. Dawe and co-workers (1-6) have obtained a fraction from the blood of hibernating woodchucks and ground squirrels ("trigger") that, when injected into alert ground squirrels, induces hibernation even in the summer. Other researchers have failed to obtain a significant induction of hibernation in squirrels (7,8) or hamsters (9) using a similar protocol. Swan et al (10-13) have prepared extracts of brains obtained from hibernating or aestivating animals that have been reported to cause a decline in both body temperature and oxygen consumption when injected intravenously into rats. The large quantities of brain extract required to elicit a response in rats precluded the use ofthis whole animal assay in isolating the factor responsible for lowering metabolic rates. In the present study we have developed a sensitive cell culture bioassay capable ofdistinguishing between extracts prepared from brains of hibernating and alert ground squirrels. Although the levels ofthe active substance in the extract correlate with entrance into hibernation, a similar activity can be detected in brain extracts ofhomeotherms where the levels ofthe active agent respond to altered environmental conditions. The nature of the active substance and the cellular response to it have been investigated. Brains, obtained from animals sacrificed by decapitation, were removed immediately and frozen in either liquid nitrogen or acetone and dry ice. Cold-acclimated squirrels were maintained at 80C and had been in hibernation previously but were not in hibernation on the day ofsacrifice. Hibernating squirrels were also maintained at 80C and had been in hibernation on the observation day previous to the day of sacrifice (2-3 days earlier). Squirrels that were entering hibernation were...

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“…The internal (bio)chemical trigger responsible for the subsequent propagation of this signal is key to understanding the hibernation process. It has been suggested that a yet to be characterized endogenous molecular compound, referred to as hibernation induction trigger (HIT), is responsible for inducing hibernation in vivo [59,60] via the Rx-Q(-Tb) relationship, whereby the drop in Tb is arguably a consequence of the reduced Q by the HIT (Figure 7). It should be noted that this mechanism would differ fundamentally from anapyrexic signaling, which requires Ztn downmodulation and subsequent Ta-Tb equalization as a precursor event for hypometabolic induction ( Figure 6).…”

Section: Pharmacological Agents and Induction Of Artificial Hypometabmentioning

confidence: 99%

“…It should be noted that this mechanism would differ fundamentally from anapyrexic signaling, which requires Ztn downmodulation and subsequent Ta-Tb equalization as a precursor event for hypometabolic induction ( Figure 6). In an effort to identify the HIT, different endogenous compounds have been investigated that have potential to account for or mimic the effect of the HIT, including H2S [3], 5'-adenosine monophosphate (5'-AMP) [61], thyronamines (TAMs) [6], 2'-deoxyglucose (2-DG) [4], and delta-opioids (DOPs) [5,59]. Although induction of a hypometabolic state is a shared trait of these agents, each is associated with a different pattern of physiological effects.…”

Section: Pharmacological Agents and Induction Of Artificial Hypometabmentioning

confidence: 99%

The physiology of artificial hibernation

Heger

2015

JCTRes

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Incomplete understanding of the mechanisms responsible for induction of hibernation prevent translation of natural hibernation to its artificial counterpart. To facilitate this translation, a model was developed that identifies the necessary physiological changes for induction of artificial hibernation. This model encompasses six essential components: metabolism (anabolism and catabolism), body temperature, thermoneutral zone, substrate, ambient temperature, and hibernation-inducing agents. The individual components are interrelated and collectively govern the induction and sustenance of a hypometabolic state. To illustrate the potential validity of this model, various pharmacological agents (hibernation induction trigger, delta-opioid, hydrogen sulfide, 5'-adenosine monophosphate, thyronamine, 2-deoxyglucose, magnesium) are described in terms of their influence on specific components of the model and corollary effects on metabolism. Relevance for patients: The ultimate purpose of this model is to help expand the paradigm regarding the mechanisms of hibernation from a physiological perspective and to assist in translating this natural phenomenon to the clinical setting.

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Hibernation Induced in Ground Squirrels by Blood Transfusion

Cited by 106 publications

References 0 publications

Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

Extracts from the brains of hibernating and alert ground squirrels: effects on cells in culture.

The physiology of artificial hibernation

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