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PubMed1992

Suppression of guinea pig ileum induced contractility by plasma albumin of hibernators.

Previous studies suggest that hibernation may be regulated by internal opioids and that the putative "hibernation induction trigger" (HIT) may itself be an opioid. This study examined the effect of plasma albumin (known to bind HIT) on induced contractility of the guinea pig ileum muscle strip. Morphine (400 nM) depressed contractility and 100 nM naloxone restored it. Ten milligrams of lyophilized plasma albumin fractions from hibernating ground squirrels, woodchucks, black bears, and polar bears produced similar inhibition, with partial reversal by naloxone. Five hundredths mg of D-Ala2-D-Leu5-enkephalin (DADLE) also inhibited contractility and naloxone reversed it. Conclusions are that hibernating individuals of these species contain an HIT substance that is opioid in nature and summer animals do not; an endogenous opioid similar to leu-enkephalin may be the HIT compound or give rise to it.

Animals↗
PubMed1990

Hibernation activates glyoxylate cycle and gluconeogenesis in black bear brown adipose tissue.

Biochemical studies on brown adipose tissue removed from a hibernating black bear and a non-hibernating control animal demonstrate that this tissue: (1) can carry out cyanide-insensitive fatty acid oxidation, and (2) possesses catalase activity and the enzyme activities unique to the glyoxylate cycle, isocitrate lyase and malate synthase. These activities are all markedly increased in brown fat obtained from the hibernating animal. Additionally, hibernation enhances the ability of the tissue to synthesize glycogen in the presence of a fatty acid substrate. The glyoxylate cycle enzymes and the ability to convert fatty acid carbons to glucose have been generally regarded as being absent from vertebrate cells and tissues.

Adipose Tissue, Brown↗
PubMed1983

Hibernation-hypothermia and metabolism in hedgehogs. Changes in water and electrolytes.

1. Hedgehogs seem not to suffer water loss during hibernation or hypothermia probably through water shifts from the interstitium to the cells and/or protein catabolism in tissues. 2. Higher potassium concentrations were retained in hedgehog's tissues, sodium and chloride ions rose in plasma, but ionic gradients were slightly affected. Probable reasons for increased calcium, magnesium and inorganic phosphorus were discussed. 3. Changes recorded during late fall indicated the predisposition of animals to hibernate, while changes during spontaneous and full arousals showed a reversed phenomenon in the hibernation cycle. 4. Artificially hypothermic animals in summer showed results similar to those of naturally hypothermic in winter, although lower in magnitude, suggesting a specific role of temperature in regulating the hibernation cycle.

Animals↗
PubMed1988

The intestinal epithelial cells of ground squirrel (Citellus undulatus) accumulate at G2 phase of the cell cycle throughout a bout of hibernation.

1. The mitotic index was found to be greatly reduced in the intestinal crypt cells of ground squirrel during bout of hibernation. The percentage of mitosis rose abruptly at least 2 hr after arousal. 2. An increase in the number of G2 cells was found in the intestinal tract of ground squirrel during bouts of hibernation. 3. The conclusion can be drawn that the cells are progressing steadily through the cell cycle. The cells accumulate at G2 in hibernation. 4. It was assumed that the block in G2 prevents the cells from possible damage in mitosis under hypothermia accompanying hibernation and, therefore, it represents an adaptive reaction.

Animals↗
PubMed1989

Hibernation in a monotreme, the echidna (Tachyglossus aculeatus).

The body temperatures of five echidnas in Australia's Southern Alps were monitored by radio telemetry from February to December 1987. All five hibernated throughout the winter, showing very low body temperatures (4-9 degrees C, close to ambient) when torpid, compared with 28-33 degrees C in a typical day during the active season. Spontaneous arousals from hibernation occurred every 2-3 weeks, during which body temperatures rose rapidly to over 30 degrees C for several hours before dropping to be close to ambient again. The identification of "classical" hibernation in a monotreme, with a similar pattern to that seen in Eutheria and in an animal as large as the largest eutherian hibernator, has important implications for current ideas about the evolution of endothermy.

Animals↗
PubMed1993

The effects of short term cold storage upon ATP and 2,3-BPG levels in the blood of euthermic and hibernating thirteen-lined ground squirrels Spermophilus tridecemlineatus.

1. Whole blood was collected from hibernating and euthermic ground squirrels. 2. Blood from hibernating animals had approximately 50% less ATP and 2,3-biphosphoglycerate (2,3-BPG) than did that from euthermic animals. 3. In euthermic blood subjected to in vitro cold storage, levels of ATP decreased to those observed in hibernators, but 2,3-BPG did not decline significantly. 4. During cold storage of hibernator blood, no significant changes occurred in levels of these organophosphates.

2,3-Diphosphoglycerate↗
PubMed1989

Membrane function in mammalian hibernation.

For homeotherms the maintenance of a high, uniform body temperature requires a constant energy supply and food intake. For many small mammals, the loss of heat in winter exceeds energy supply, particularly when food is scarce. To survive, some animals have developed a capacity for adaptive hypothermia in which they lower their body temperature to a new regulatory set-point, usually a few degrees above the ambient. This process, generally known as hibernation, reduces the temperature differential, metabolic activity, as well as the energy demand, and thus facilitates survival during winter. Successful hibernation in mammals requires that the enzymatic processes are regulated in such a manner that metabolic balance is maintained at both the high body temperature of the summer-active animal (37 degrees C) and the low body temperature of the winter-torpid animal (approx. 5 degrees C). This means that the cellular membranes have thermal properties capable of maintaining a balanced metabolism at these extreme physiological temperatures. The available evidence indicates that, for some tissues, preparation for hibernation involves an alteration in the lipid composition and thermal properties of cellular membranes. Marked differences in the thermal response of cellular membranes have been observed on a seasonal basis and, in some membranes, differences in lipid composition have been associated with the torpid state. However, to date, no consistent changes in lipid composition which would account for, or explain, the changes in membrane thermal response, have been detected. An important point to emphasize is that the process of 'homeoviscous adaptation', which occurs in procaryotes and some poikilotherms during acclimation to low temperatures, is not a characteristic feature of most membranes of mammalian hibernators.

Animals↗
PubMed1978

Enzymes of heterotherms: LDH of hibernating and normothermic little brown bats, Myotis lucifugus.

1. Lactate dehydrogenase (LDH) was isolated from pectoral or flight muscle, liver and heart of hibernating and normothermic bats, Myotis lucifugus. 2. Activities at high substrate concentrations and the interactions between substrate and enzyme were studied to evaluate possible adaptations associated with the extended period of depressed metabolism of this bat. 3. Activity levels in all tissues decreased with hibernation, although the magnitude was dependent upon both temperature and substrate concentration. In general, the extent of decrease was in the order pectoral muscle greater than liver much greater than heart. 4. No correlation was found between the temperature sensitivity of the tissue LDHs as estimated by Ea-values, and the physiological state. 5. However, affinity parameters as estimated by Km-values were less temperature sensitive in hibernator tissues in contrast to the marked perturbations exhibited at temperature extremes in the normotherm enzymes. 6. It is suggested that changes in subunit quantities are in part responsible for these kinetic differences, and not major qualitative isozyme changes. 7. The net result of these effects is a reduced carbon flux to lactate during hibernation, but the maintenance of a potential for LDH catalyses during arousal.

Animals↗
PubMed1978

Variations in (Na+ + K+)-ATPase and Mg2+-ATPase activity of the ground squirrel brain during hibernation.

1. The specific activity of brain (Na+ + K+)-ATPase and Mg2+ -ATPase of the ground squirrel (Spermophilus richardsonii) is significantly increased after long-term hibernation. 2. The markedly non-linear thermal dependence of (Na+ + K+)-ATPase is unchanged during hibernation whereas the near linear thermal dependence of Mg2+-ATPase undergoes minor alteration after prolonged hibernation. 3. The sensitivity of (Na+ + K+)-ATPase to inhibition by ouabain is significantly decreased after 100 days of hibernation as is both the rate and amount of [3H]-ouabain binding. 4. These changes may be related to alteration in the phospholipid matrix of the membrane rather than alteration in the protein structure of the enzyme.

Animals↗
PubMed1983

Distribution of superoxide dismutase in the ground squirrel (Citellus citellus): effect of the hibernation and arousal.

The activity of superoxide dismutase (SOD) was studied in the liver, kidney, interscapular brown adipose tissue (IBAT), lung, heart and spleen of the active and hibernating ground squirrel (Citellus citellus). One group was examined immediately after the arousal from the hibernation. A considerable activity of this enzyme was found in homogenates of all tissues studied except the lung. This activity was lower in the liver and lung of the ground squirrel than in the rat (P less than 0.01). In the other tissues studied the enzyme activity was about the same level in both animals. In the ground squirrel hibernation didn't produce the significant change in SOD activity, as compared with the active state, except in the spleen. Tested immediately after the arousal, SOD activity was significantly higher in all tissues studied except in the IBAT, as compared with the hibernating ones (P less than 0.01).

Animals↗
PubMed1984

Effect of hibernation on liver and kidney metabolism in 13-lined ground squirrels.

Metabolic rates and adenine nucleotide content of liver and kidney from hibernating ground squirrels were measured and compared to rats to study the biochemical adaptation to hibernation. High rates of renal and hepatic gluconeogenesis were observed in squirrels, particularly from propionate and glycerol compared to rat. During hibernation and starvation soluble phosphoenolpyruvate carboxykinase activity was increased in both liver and kidney. Although metabolic rates are decreased during hibernation the results suggest that the enzymic complement is maintained at high activity even during torpor.

Adenine Nucleotides↗
PubMed1992

Analysis of the causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers, Citellus undulatus.

1. The causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers have been analysed. 2. The decrease of the ATP synthesis rate and suppression of the energy-dependent K(+)- and Ca(2+)-transport into mitochondria during hibernation has been found to be mainly related to a delta psi decrease in mitochondria of hibernating gophers. 3. The increase delta psi upon incubation of the mitochondria of hibernating animals in a hypotonic medium results in an essential acceleration of ATP synthesis and energy-dependent cationic transport.

Adenosine Triphosphate↗
PubMed1995

Changes in various plasma lipid components, glucose, and insulin in Spermophilus lateralis during hibernation.

This study evaluated fat mobilization as related to gluconeogenesis in two age groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis). Our experimental group consisted of a total of 16 male and 15 female squirrels. Plasma samples were collected from selected animals being killed weekly from January to March, and the concentration of triglycerides, glycerol (GY), free fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were determined by biochemical assays and radioimmunoassay. Our results showed a mean FFA/GY ratio of five, which was higher than the predicted value of three, suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis via GY to maintain glucose homeostasis in the hibernating animals. The factor of age did not significantly affect plasma lipid components. However, in the male group, plasma glucose levels were significantly higher for adults than for juveniles. Overall, females had significantly higher plasma glucose levels than males (150 +/- 11 vs. 110 +/- 8 mg%, P < 0.05). In the adult group, a gender influence was also seen on plasma insulin levels, with females' being higher than males' (66 +/- 13 vs. 25 +/- 3 microIU/ml, P < 0.01). We suggest that during hibernation, female squirrels may have a higher rate of lipolysis and gluconeogenesis along with a lower glucose utilization than their male counterparts. Additionally, adult females may exhibit a higher peripheral insulin resistance during hibernation than adult males, a possibility which merits further study.

Age Factors↗
PubMed1981

Hibernation "trigger" injected in brain induces hypothermia and hypophagia in the monkey.

In ovariectomized adult female macaque monkeys, cannulae were affixed bilaterally to the skull for intracerbroventricular injection. Baseline temperature, heart rate, food and water intakes were monitored in each animal after it had been acclimatized to a primate restraining chair. Lyophilized serum albumin fractions extracted from the blood of hibernating woodchucks or summer active, nonhibernating woodchucks were reconstituted in an artificial CSF. Following the intracerebroventricular injection of 3.0 to 4.0 mg of hibernating woodchuck albumin (HWA) in a volume of 300 to 400 microliters, a decline in the temperature of the monkey occurred which varied in magnitude and duration. A marked inhibition of food intake, accompanied by a decline in prandial water intake, persisted for 24 to 36 hours. This hypophagia was due mainly to a reduction in the number of feeding episodes during the periods of observation. Although heart rate declined intermittently, respiratory rates remained unchanged. Summer active woodchuck albumin (SAWA) or bovine serum albumin (BSA) given in the identical range of doses, as well as artificial CSF, exerted little or no effect either on body temperature of the primate or on its food intake. These results demonstrate for the first time that a plasma "trigger" factor, obtained from a hibernating animal in torpor, exerts a direct physiological action on the brain of a mammal which is incapable of entering into hibernation. Vital metabolic, thermoregulatory and other control processes mediated by diencephalic and other systems in the CNS are directly suppressed by the "trigger" factor. The clinical implications of these findings are presented.

Animals↗
PubMed1990

Antioxidant defenses in the ground squirrel Citellus citellus. 2. The effect of hibernation.

In spring and autumn, the ground squirrel Citellus citellus is awake and active but in winter it usually hibernates. Reawakening from hibernation involves intense metabolic activity in the interscapular brown adipose tissue (IBAT). The IBAT of hibernation animals showed significant increases in the activities of superoxide dismutase (both copper-zinc and manganese-containing enzymes), glutathione peroxidase, and in the amount of ascorbate present. Glutathione peroxidase also increased in the liver, as did ascorbate in the plasma. These changes were not merely a consequence of exposure to low environmental temperatures. It is proposed that antioxidant defenses are increased in the IBAT of ground squirrels at the onset of hibernation in order to protect the tissue from reactive oxygen species generated as a result of the intense metabolic activity sustained by this tissue during reawakening.

Adipose Tissue, Brown↗
PubMed2006

Cloning and expression of PDK4, FOXO1A and DYRK1A from the hibernating greater horseshoe bat (Rhinolophus ferrumequinum).

Pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) cDNA was cloned from the brain of greater horseshoe bat (Rhinolophus ferrumequinum). The deduced amino acid sequence shares strong homology with these PDK4 of other mammals. Moreover, we partially cloned homologues of dual-specificity tyrosine-phosphorylated and regulated protein kinase 1A (DYRK1A), and forkhead box protein O1A (FOXO1A) from greater horseshoe bat. Among five different tissues tested, PDK4 mRNA was highly expressed in the heart, white adipose tissue and muscle, but weakly expressed in the brain and liver, while DYRK1A and FOXO1A were expressed in all five tissues. Moreover, the transcript levels of PDK4, DYRK1A, and FOXO1A were measured in the heart, white adipose tissue and muscle of hibernating and arousal greater horseshoe bats by Northern blot and real time PCR. The results showed that transcript level of PDK4 was significantly higher in white adipose tissue. Expression level of DYRK1A was significantly higher in hibernating state in white adipose tissue, and expression level of FOXO1A was significantly higher in muscle in aroused state. These results suggest that up-regulation of the transcript levels of PDK4 during hibernation were not regulated via DYRK1A and FOXO1A in white adipose tissue and muscle, and the possible presence of another isoenzyme of PDK which is responsible for the tissue-specific regulation of Pyruvate dehydrogenase complex (PDC) activity in the bat heart during hibernation.

Animals↗
PubMed2005

Ground squirrel splenic macrophages bind lipopolysaccharide over a wide range of temperatures at all phases of their annual hibernation cycle.

This study evaluates binding of bacterial lipopolysaccharide (LPS) by splenic macrophages from golden-mantled ground squirrels (Spermophilus lateralis, GMGS), a hibernating mammal, at a variety of in vitro incubation temperatures to determine whether this aspect of immune function is effective at low body temperatures. LPS-binding by ground squirrel macrophages was compared to that of rat splenic macrophages. Macrophages were collected from squirrels at discreet stages in their annual cycle and incubated with fluorescein-labeled LPS (LPS-FITC). The percentage of GMGS that bound LPS-FITC did not change as a function of hibernation season or as a function of incubation temperature. The total amount of LPS-FITC bound per cell was similarly unaffected by season or temperature, however, macrophages from torpid squirrels bound more LPS-FITC than cells from normothermic squirrels. Macrophages of golden-mantled ground squirrels bind LPS at a wide range of temperatures throughout their annual cycle; an ability shared between hibernators and non-hibernators alike.

Animals↗
PubMed2005

The tensile strength of black bear (Ursus americanus) cortical bone is not compromised with aging despite annual periods of hibernation.

Black bears (Ursus americanus) may not develop disuse osteoporosis during long periods of disuse (i.e. hibernation) because they may be able to maintain bone formation. Previously, we found that cortical bone bending strength was not compromised with age in black bears' tibias, despite annual periods of disuse. Here we showed that cortical bone tensile strength (166-198MPa) also does not decrease with age (2-14 years) in black bear tibias. There were also no significant age-related changes in cortical bone porosity in black bear tibias. It is likely that the ability of black bears to maintain bone formation during hibernation keeps bone porosity low (2.3-8.6%) with aging, notwithstanding annual periods of disuse. This low porosity likely preserves ultimate stress with aging. Female bears give birth and nurse during hibernation; however, we found no significant differences between male and female tensile material properties, mineral content, or porosity. Our findings support the idea that black bears, which hibernate 5-7 months annually, have evolved biological mechanisms to mitigate the adverse effects of disuse on bone porosity and strength.

Aging↗