Absence of evidence for a hibernation “trigger” in blood dialyzate of Richardson's ground squirrel

Abbotts, Bruce; Wang, Lawrence C.H.; Glass, J.David

doi:10.1016/0011-2240(79)90029-4

Cited by 17 publications

(10 citation statements)

References 11 publications

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“…3 will clarify how complex adaptive behaviors arise during evolution. In addition, it may be possible to work backwards from the hibernationinduced differential expression of liver genes, such as that of a2-macroglobulin, demonstrated here, to the putative master controller-i.e., the elusive (27,28) trigger molecule (29)--of hibernation.…”

Section: Resultsmentioning

confidence: 99%

Central role for differential gene expression in mammalian hibernation.

Srere

Wang

Martin

1992

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

144

105

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Mammalian hibernators experience dramatic reductions in body temperature, metabolic rate, respiratory rate, and heart rate during hibernation. These changes are precisely controlled and reversible with only internally driven mechanisms, suggesting specific biochemical regulation. We present a model that integrates our observations of differential liver gene expression during preparation for, and maintenance of, the hibernating state, with the known phylogenetic interspersion of hibernating species in several major mammalian lineages. This model predicts a major role for the differential expression of existing mammalian genes in the biochemical regulation of hibernation.Hibernation is an adaptive strategy that is used by species in several mammalian orders to conserve energy in cold or inhospitable environments. During hibernation, these mammals dramatically lower their metabolic, heart, and respiratory rates as well as their body temperature in a precisely controlled manner. This strategy helps some, particularly small, mammals to survive cold winter conditions in temperate climates when food and water are scarce yet the demand for metabolic heat generation is high. Hibernating species are frequently closely related to nonhibernating species and are found in five orders of eutherian mammals as well as in a few species of marsupials and monotremes (ref. 1 and Fig. 1). The adaptive significance of hibernation, coupled with the interspersed phylogenetic distribution of hibernating species among mammals, makes hibernation an ideal model system to test the hypothesis that the molecular basis of important adaptive events during evolution involves mechanisms that lead to the differential regulation of existing genes and not the invention of new genes (reviewed in ref.3).The evolutionary origin of hibernation is unknown; either of two hypotheses can explain the interspersed nature of the distribution of extant hibernating species throughout Mammalia. One postulates that the common ancestor of all mammals was a hibernator, but the ability to hibernate was lost independently along multiple lineages. The alternative proposes that the common ancestor of all mammals was not a hibernator, and the ability to hibernate has been gained independently along multiple lineages (Fig. 1). With either scenario, we predict that a small number of regulatory changes determine the phenotype of hibernation, rather than the de novo creation or loss of numerous hibernation-specific biochemical functions, encoded by a collection of hibernation-specific genes. Thus, hibernation must be the result of a reprogramming of existing mammalian biochemical capabilities through the differential expression of existing genes.There is little evidence in the literature for differential gene expression during hibernation, although there are a few reports that demonstrate increases or decreases (4) in the amount of specific proteins relative to the active state. Mitochondrial uncoupling protein (thermogenin) is an example of a protein that increases i...

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Section: Resultsmentioning

confidence: 99%

Central role for differential gene expression in mammalian hibernation.

Srere

Wang

Martin

1992

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

144

105

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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: 69%

“…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)(11)(12)(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.…”

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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“…When serum or plasma taken during hibernation from several species of ground squirrels and the woodchuck is transfused into active 13-lined ground squirrels, hibernation is induced in the recipients during the summer, at a time when hibernation is normally absent (Dawe 1978;Oeltgen and Spurrier 1981). However, using a similar approach but with other species of ground squirrels (Galster 1978;Abbotts et al 1979) or hamsters (Minor et al 1978), each serving as both the donor and the recipient, summer hibernation cannot be induced. These variant results seem to suggest that a species specificity may exist in the recipient but not in the donor (Abbotts et al 1979).…”

Section: The "Hibernation Induction Trigger"mentioning

confidence: 96%

“…However, using a similar approach but with other species of ground squirrels (Galster 1978;Abbotts et al 1979) or hamsters (Minor et al 1978), each serving as both the donor and the recipient, summer hibernation cannot be induced. These variant results seem to suggest that a species specificity may exist in the recipient but not in the donor (Abbotts et al 1979). This possibility has recently been extensively investigated in my laboratory involving two series of experiments (Wang, Lee, Jourdan, Westly, Niirnberger, and Belke, unpubl.).…”

Section: The "Hibernation Induction Trigger"mentioning

confidence: 96%

Mammalian Hibernation: An Escape from the Cold

Wang

1988

Advances in Comparative and Environmental Physiology

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Absence of evidence for a hibernation “trigger” in blood dialyzate of Richardson's ground squirrel

Cited by 17 publications

References 11 publications

Central role for differential gene expression in mammalian hibernation.

Central role for differential gene expression in mammalian hibernation.

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

Mammalian Hibernation: An Escape from the Cold

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