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PubMed1992

Effects of fasting and hibernation on ion secretion in ground squirrel intestine.

Ground squirrels were used to study the effects of fasting and hibernation on small intestinal secretory function. Muscle-stripped sheets of jejunum set up in flux chambers were challenged with a variety of secretory agonists, and changes in short-circuit current (Isc) were recorded. Mucosal wet weights per centimeter and crypt dimensions were not affected by a 3-day fast in active squirrels, but villus height and area were significantly reduced in hibernators that had not eaten for over 6 wk. Tissue conductance was significantly greater in fasted and hibernating squirrels compared with fed animals. Maximal changes in Isc evoked by electrical stimulation of submucosal neurons, normalized to serosal surface area, were greater in fasted compared with fed or hibernating squirrels. When responses were normalized to crypt area, neurally evoked changes in Isc were greatest in the hibernators. Carbachol and serotonin evoked dose-dependent changes in Isc that were greater in fasted compared with fed squirrels at all concentrations. Histamine (100 microM) and theophylline (1 mM) also produced greater increases in Isc in fasted than in fed squirrels. The results suggest that a 3-day fast, or the extended fast of hibernation, results in enhanced secretory capacity in the ground squirrel jejunum.

Animals↗
PubMed1996

Gonadectomy in the spring reinstates hibernation in male golden-mantled ground squirrels.

We tested the hypothesis that continued secretion of gonadal steroids is necessary to suppress hibernation in male golden-mantled ground squirrels in the weeks after the terminal arousal in spring. Juvenile and adult males were gonadectomized or sham gonadectomized 1 wk after the terminal arousal; 64% of castrated and none of the shamcastrated animals resumed hibernation. Latency to resumption of torpor was 9 +/- 2 days from the time of castration, and squirrels underwent 4.3 +/- 0.9 bouts before permanently regaining euthermia. Among squirrels that resumed hibernation, bout duration was significantly shorter and torpor was shallower after castration. Castration as late as 3 wk after the terminal arousal reinstated hibernation. We suggest that the terminal arousal of male squirrels in the spring is provoked by a steroid-independent mechanism similar to that operating earlier in the hibernation season; abandonment of hibernation is contingent on concomitant sustained increases in androgen secretion during the first few weeks of euthermia.

Aging↗
PubMed1997

Serotonergic modulation of hippocampal pyramidal cells in euthermic, cold-acclimated, and hibernating hamsters.

Serotonergic fibers project to the hippocampus, a brain area previously shown to have distinctive changes in electroencephalograph (EEG) activity during entrance into and arousal from hibernation. The EEG activity is generated by pyramidal cells in both hibernating and nonhibernating species. Using the brain slice preparation, we characterized serotonergic responses of these CA1 pyramidal cells in euthermic, cold-acclimated, and hibernating Syrian hamsters. Stimulation of Shaffer-collateral/commissural fibers evoked fast synaptic excitation of CA1 pyramidal cells, a response monitored by recording population spikes (the synchronous generation of action potentials). Neuromodulation by serotonin (5-HT) decreased population spike amplitude by 54% in cold-acclimated animals, 80% in hibernating hamsters, and 63% in euthermic animals. The depression was significantly greater in slices from hibernators than from cold-acclimated animals. In slices from euthermic animals, changes in extracellular K+ concentration between 2.5 and 5.0 mM did not significantly alter serotonergic responses. The 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin mimicked serotonergic inhibition in euthermic hamsters. Results show that 5-HT is a robust neuromodulator not only in euthermic animals but also in cold-acclimated and hibernating hamsters.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1977

Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia.

Mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia were investigated through measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output. Hamsters (Mesocricetus auratus) were made hypothermic (rectal temperature (Tre), 7 degrees C) by exposure to helox and cold, or permitted to hibernate with several weeks of cold exposure (Ta approximately 5 degrees C). Mean arterial pressure, 120 Torr in normothermic control animals, demonstrated a 55% and 60% decrease during hibernation and hypothermia, respectively. As the animals rewarmed from hypothermia or aroused from hibernation, blood pressure increased rapidly at 8-12 degrees C, more gradually at 12-17 degrees C, and plateaued thereafter. Blood pressure rapidly returned to near control levels whereas heart rate remained at less than one-half control value at the highest temperature examined. Red blood cell volume, 26.2 +/- 0.6 ml/kg body wt in the control animals appeared unaffected by hypothermia. Plasma volume, by contrast, decreased from control values of 33.0 +/- 0.8 to 21.3 +/- 0.6 ml/kg body wt in hypothermia, a decrease of approximately 35%. Distribution of cardiac output to various organs in hibernation and hypothermia followed a similar pattern. Relative flow to the heart, lung, diaphragm, and brown fat increased while the fraction distributed to the visceral organs appeared to decrease. The normothermic control kidney received approximately 16% of the cardiac output while the hibernating and hypothermic kidneys received approximately 10% and 6%, respectively. The data are discussed in terms of the determinants of glomarular filtration rate and explain, in part, the elimination or marked reduction in renal function observed in depressed metabolic states.

Animals↗
PubMed2003

Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis).

BACKGROUND: Jerboa (Jaculus orientalis) is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc) and D-3-hydroxybutyrate (BOH) are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH) E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process. RESULTS: We found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respectively for AcAc reduction and for BOH oxidation. The same differences were found in the hibernation state. 2/ In euthermic jerboa, the Michaelis constants, KM BOH and KM NAD+ are different in liver and in brain while KM AcAc, KM NADH and the dissociation constants, KD NAD+and KD NADH are similar. 3/ During prehibernating state, as compared to euthermic state, the liver BDH activity is reduced by half, while kinetic constants are strongly increased except KD NAD+. 4/ During hibernating state, BDH activity is significantly enhanced, moreover, kinetic constants (KM and KD) are strongly modified as compared to the euthermic state; i.e. KD NAD+ in liver and KM AcAc in brain decrease 5 and 3 times respectively, while KD NADH in brain strongly increases up to 5.6 fold. 5/ Both protein content and mRNA level of BDH remain unchanged during the cold adaptation process. CONCLUSIONS: These results cumulatively explained and are consistent with the existence of two BDH enzymatic forms in the liver and the brain. The apoenzyme would be subjected to differential conformational folding depending on the hibernation state. This regulation could be a result of either post-translational modifications and/or a modification of the mitochondrial membrane state, taking into account that BDH activity is phospholipid-dependent.

Animals↗
PubMed2002

Adaptive mechanisms of intracellular calcium homeostasis in mammalian hibernators.

Intracellular Ca(2+) homeostasis is a prerequisite for a healthy cell life. While cells from some mammals may suffer dysregulation of intracellular Ca(2+) levels under certain deleterious and stressful conditions, including hypothermia and ischemia, cells from mammalian hibernators exhibit a remarkable ability to maintain a homeostatic intracellular Ca(2+) environment. Compared with cells from non-hibernators, hibernator cells are characterized by downregulation of the activity of Ca(2+) channels in the cell membrane, which helps to prevent excessive Ca(2+) entry. Concomitantly, sequestration of Ca(2+) by intracellular Ca(2+) stores, especially the sarcoplasmic/endoplasmic reticulum, is enhanced to keep the resting levels of intracellular Ca(2+) stable. An increase in stored Ca(2+) in heart cells during hibernation ensures that the levels of Ca(2+) messenger are sufficient for forceful cell contraction under conditions of hypothermia. Maintenance of Na(+) gradients, via Na(+)-Ca(2+) exchangers, is also important in the Ca(2+) homeostasis of hibernator cells. Understanding the adaptive mechanisms of Ca(2+) regulation in hibernating mammals may suggest new strategies to protect nonhibernator cells, including those of humans, from Ca(2+)-induced dysfunction.

Adaptation, Physiological↗
PubMed2005

A novel phenomenon predicting the entry into a state of hibernation in Syrian hamsters (Mesocricetus auratus).

When Syrian hamsters (Mesocricetus auratus) are bred in a cold and short-day environment, most animals go into hibernation after a certain period of time. However, to date it has not been possible to predict which hamster will enter hibernation. In this study, we subcutaneously implanted thermo-loggers in hamsters bred in the cold environment, and recorded the subcutaneous temperature at short intervals until they went into hibernation. A time series analysis of temperature disclosed that a fall of 0.4 to 0.8 degrees C in subcutaneous temperature was seen 5 to 16 days before entering hibernation, and this phenomenon continued for three days or more. No hamster went into the hibernation without displaying this signal. Although the mechanism by which this phenomenon takes place is not clear, it is a sign from the body, which is useful for indicating if a hamster will enter hibernation shortly.

Acclimatization↗
PubMed1986

Copper-zinc containing and manganese containing superoxide dismutase in the ground squirrel/Citellus citellus/--the effect of hibernation.

The distribution of Copper-Zinc containing and Manganese-containing superoxide dismutase in the liver, kidney, interscapular brown adipose tissue (IBAT) and brain of the ground squirrel, as well as the effect of hibernation, was studied. Activity of both forms of SOD was highest in the liver and lowest in the brain. Activity of the Mn SOD in relation to total SOD was higher in the liver and kidney of the ground squirrel as compared with results reported for other rodents. The highest activity of Mn SOD in relation to total SOD was found in the IBAT and brain (36% and 49%, respectively). Total SOD activity per mg proteins and per g wet mass in IBAT and brain of hibernating animals was increased: for IBAT, p less than 0.05 and p less than 0.025, respectively; for brain, p less than 0.01 and p less than 0.025, respectively. Protein content in hibernating ground squirrel was not significantly changed. In the hibernating ground squirrel CuZn SOD activity in IBAT and brain was higher as compared with the active animal (p less than 0.025 and p less than 0.005, respectively). In the liver and kidney CuZn SOD was not significantly changed during the hibernation. In the liver and brain of the hibernating animals a lower Mn SOD activity was found (p less than 0.005 and p less than 0.05, respectively).

Adipose Tissue, Brown↗
PubMedDate not supplied

[The Van't Hoff rule in studying various phases of hibernation of the squirrel Citellus undulatus Pallas. Physico-chemical route to cold adaptation].

Taking into account the van't Hoff's law the rates of relative erythrocyte hemolysis in ground squirrel Citellus undulatus Pallas during different phases of hibernation were first studied by the method of acid erythrograms with some modifications. The temperature of the erythrogram registration (8 degrees C) models the body temperature in hibernation, and temperature of 35 degrees C, corresponds to the body temperature of the awakened ground squirrel. The positions of the erythrogram maxima for the ground squirrel during short-term arousal and during hibernation coincide for each temperature studied: 8 or 35 degrees C. Therefore, the increase in HCl concentration at 8 degrees C reflects an increase in the stability of erythrocyte membranes or a decrease in the rate of relative hemolysis for the ground squirrel during hibernation. Thus, the adaptive response of erythrocytes in hibernating ground squirrel is revealed. The correlation of the rates of physicochemical processes in vitro with the rates of physiological ones in vivo is shown using the ratio of the rates mentioned above for the short-term arousal and for hibernation. First the physicochemical way of cold adaptation due to the van't Hoff's law is proved.

Adaptation, Physiological↗
PubMed2001

Glutamate dehydrogenase from liver of euthermic and hibernating Richardson's ground squirrels: evidence for two distinct enzyme forms.

Glutamate dehydrogenase (GDH) was purified to homogeneity from the liver of euthermic (37 degrees C body temperature) and hibernating (torpid, 5 degrees C body temperature) Richardson's ground squirrels (Spermophilus richardsonii). SDS-PAGE yielded a subunit molecular weight of 59.5+/-2 kDa for both enzymes, but reverse phase and size exclusion HPLC showed native molecular weights of 335+/-5 kDa for euthermic and 320+/-5 kDa for hibernator GDH. Euthermic and hibernator GDH differed substantially in apparent Km values for glutamate, NH4+, and alpha-ketoglutarate, as well as in Ka and IC50 values for nucleotide and ion activators and inhibitors. Kinetic properties of each enzyme were differentially affected by assay temperature (37 versus 5 degrees C). For example, the Km for alpha-ketoglutarate of euthermic GDH was higher at 5 degrees C (3.66+/-0.34 mM) than at 37 degrees C (0.10+/-0.01 mM), whereas hibernator GDH had a higher affinity for alpha-ketoglutarate at 5 degrees C (Km was 0.98+/-0.08 mM at 37 degrees C and 0.43+/-0.02 mM at 5 degrees C). Temperature effects on Ka ADP values of the enzymes followed a similar pattern; GTP inhibition was strongest with the euthermic enzyme at 37 degrees C and weakest with hibernator GDH at 5 degrees C. Entry into hibernation leads to stable changes in the properties of ground squirrel liver GDH that allow the enzyme to function optimally at the prevailing body temperature.

Animals↗
PubMedDate not supplied

[Properties of C protein from skeletal and cardiac muscles of the ground squirrel Citellus undulatus at various stages of hibernation].

Changes in the molecular weight and functional properties of the C and X proteins from skeletal muscles and the C protein from the cardiac muscle of hibernating ground squirrels Citellus undulatus at different stages of the hibernation were studied. A decrease in the molecular weight of the C protein from fast fibers of skeletal muscles of hibernating ground squirrels compared with awakening and active animals was revealed. The appearance of shorter molecules of the C protein upon hibernation was accompanied by a lowering of its capacity to enhance the actin-activated ATPase activity of control myosin and by the inhibition of its Ca(2+)-sensitivity. No similar changes were observed for the skeletal X protein and the cardiac C protein. The influence of the skeletal C protein on the main functional properties of myosin allows one to draw a conclusion about its contribution to the inhibition of contractile activity of skeletal muscles upon hibernation. The physiological significance of the changes in the C protein upon hibernation is discussed in connection with similar changes in some cardiomyopathies.

Actomyosin↗
PubMed1986

An autoradiographic study of the uptake of tritiated proline by osteoblasts during hibernation.

Twenty-four LSH and LVG strain golden hamsters, Mesocricetus auratus, were used. Experimental animals were maintained at 5 C and allowed to hibernate. Control animals were kept at 27 C. Six animals (3 experimental, 3 control) were injected subcutaneously with 1 microCi of 3H-proline/gm body wt. (Spec. act. 3 Ci/mM) after hibernation lasting 12 hours, 1 day, 3 days, or 7 days. Animals were killed 1 hour after injection and autoradiographs were prepared from 5 microns thick decalcified sections of femurs. A greater number of endosteal cells were labeled than periosteal cells and also exhibited a greater magnitude of labeling throughout the study. Differences between endosteal and periosteal cells both in percentage of cells labeled and magnitude of labeling were maximum in control animals and progressively decreased with increasing periods of hibernation. A reduction in synthesis of matrix proteins during the early period of hibernation was seen and was attributed to a significant reduction both in average cell activity and in the number of active cells during hibernation. The latter phenomenon apparently made a large contribution to the reduced matrical synthesis. 3H-proline uptake by osteoblasts probably reflects the reduced requirements of matrical synthesis during hibernation.

Animals↗
PubMedDate not supplied

[Features of the energy metabolism of the lizard Eremias arguta during hibernation].

During preparation to hibernation in E. arguta, fat stores increase together with glycogen content of the liver and partially of the muslces. Due to the decrease in locomotor activity of the animals, the level of unsaturated fatty acids in muscles increases. During 1- and 3-week hibernation (body temperature 2-4 degrees), glycogen of the liver and muscles is utilized. During 5-week hibernation, glycogen content of the liver and muscles increases as compared to 3-week hibernation by 3.5 and 2.3 times. In the brain the level of glycogen at all stages of hibernation is 1.4--2.1 times higher than in control animals. No accumulation in tissue lactate was observed during hibernation.

Animals↗
PubMed1995

[Changes of opioid contents in brain and plasma through the hibernation bout cycle of ground squirrels-].

Measurements of beta-endorphin (beta-EP) and Met-enkephalin (MEK) contents in various brain areas and plasma of ground squirrels were carried out by radioimmunoassay (RIA) through euthermia, entrance, deep hibernation and arousal phases of natural hibernation bout. The main results showed that, the beta-EP content in hypothalamus and pituitary during the entrance phase were increased and further deepened during deep hibernation, whereas in hippocampus and plasma the tendency of the changes of beta-EP content took place in an opposite direction, i.e. being lowered down from the euthermia level upon entering the entrance and deep hibernation phase. The content in pons and medulla showed little change through the bout. The contents of MEK were increased during entrance and lowered when entering into deep hibernation to different extent in different brain areas, being most significant change has taken place in hippocampus. These results indicated that the role of beta-EP and MEK in hibernation was different both in regard to brain regional changes of their content and in the degree of the changes.

Animals↗
PubMedDate not supplied

[ATPase and regulatory properties of skeletal muscle myosin in Citellus undulatus susliks during various stages of winter hibernation].

The paper is devoted to the study on enzymatic and regulatory properties of skeletal muscle myosin of hibernating ground squirrels (Citellus undulatus) for the purpose of elucidating the contribution of myosin and myosin filaments to the change of physiological state of the animal at the different stages of hibernation (hibernation, arousing, winter activity). It has been revealed that actin-activated ATPase activity of myosins of hibernating and arousing ground squirrels is less by 60 and 20%, correspondingly, than that of the myosin of active animals. In the absence of troponin-tropomyosin complex the Ca(2+)-sensitivity of actomyosins of the hibernating and arousing ground squirrels is less by 60 and 55%, correspondingly, than that of the actomyosin of active animals. The results obtained by us point to the essential decrease of functional properties of the main contractile protein, myosin upon hibernation, which evidently contributes to the inhibition of moving capacity of skeletal muscles at this period.

Adenosine Triphosphatases↗
PubMed1998

Bioactive peptides and serotonin immunocytochemistry in the cerebral ganglia of hibernating Helix aspersa.

The role of some neuromodulators and neurotransmitters in the functioning of molluskan cerebral neurons and in their metabolic changes during hibernation has been considered. The cerebral ganglion of mollusks is a center for the integration of different inputs from the sensory areas of the head and for the generation of motor command impulses. During hibernation, animals are deprived of many external sensory stimuli and do not have locomotion and feeding. Immunocytochemistry for bioactive peptides (BAPs), such as SP (Substance P), CCK8 (Cholecystokinin 8/Gastrin), CGRP (Calcitonin-Gene-Related Peptide) and ET (Endothelin), and serotonin was performed on cerebral ganglia of active and hibernating Helix aspersa. The distribution of the immunopositivity was analyzed in different cell-containing areas (procerebrum, mesocerebrum, metacerebrum) and in the neuropiles. With all the antibodies raised against peptides, we observed that only a few neurons, mainly of small and medium size, had immunopositivity during the period of activity, the patterns of distribution being quite similar to those previously described in Helix or other gastropods. Fibers and varicosities with BAP immunopositivity were found in the procerebral and central neuropiles and sometimes around neurons. Serotonin-immunopositive neurons, including the giant neuron, were observed in the metacerebrum; numerous fibers and varicosities immunopositive for serotonin were present in the neuropile areas. In hibernating snails, the number of fibers with BAP and serotonin immunopositivity decreased in several areas of the neuropiles. Moreover, an increased number of neurons of the metacerebrum (two-to four-fold) and mesocerebrum (8- to 28-fold) had BAP-like immunopositivity, and the intensity of the immunoreaction for serotonin of the metacerebral neurons was also higher than in the active snails. These results are discussed, taking into account two hypotheses. The first hypothesis assumes that the increased immunocytochemical staining was really linked to accumulation of BAPs and serotonin. The second hypothesis considers that the antibodies for BAPs recognized a preprotein, the synthesis of BAPs being completed during the active period only. Both the hypotheses account for the co-occurrence and co-localization of two or ore peptides and serotonin and stress that the hibernation condition is of interest for studies on the actual function of single neurons in the cerebral ganglia. Finally, the data are consistent with the changes recently found in other markers of the morphological and functional activity of neurons, demonstrating that the neuromodulation and the neurotransmission are slowed during hibernation.

Animals↗
PubMed1998

Features of short-term myocardial hibernation.

When severe ischemia, such as that resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of 'perfusion-contraction matching' exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed 'short-term hibernating myocardium'. Short-term hibernating myocardium can respond to inotropic stimulation with increased contractile function, although at the expense of renewed worsening of the metabolic status. This occurrence of increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present. Significant involvement of adenosine and activation of ATP-dependent potassium channels have been excluded. The role of triggering events and acidosis is controversial. Short-term hibernating myocardium is, however, characterized by reduced calcium responsiveness.

Acidosis↗
PubMed1998

Hibernation triggers and myocardial protection.

BACKGROUND: Hypothermic cardioplegia provides myocellular protection, yet postischemic dysfunction remains a significant problem. Interestingly, the subcellular changes in hibernation parallel the altered biology of induced cardiac ischemia but are well tolerated by hibernated mammalian myocardium. An uncharacterized factor derived from hibernating animals, hibernation induction trigger (HIT), has been shown to induce hibernation in active animals and afford myocardial protection after ischemia-reperfusion injury. Therefore, it was of interest to further characterize the cardioprotective effects of HIT in the setting of ischemia-reperfusion injury. METHODS AND RESULTS: To determine whether HIT could improve myocardial recovery after global ischemia, isolated rabbit hearts received either standard cardioplegia or HIT in the cardioplegia or underwent preperfusion with HIT before cardioplegia. Alternatively, to determine whether HIT requires metabolic alteration, additional rabbits had in vivo pretreatment with HIT from 15 minutes to 5 days before ischemia. All hearts underwent 2 hours of global ischemia at 34 degrees C. Recovery of postischemic isovolumic developed pressure, coronary flows, and MVO2 were compared. Compared with vehicle pretreatment, HIT pretreatment (1 hour) significantly enhanced indexes of functional recovery, including developed pressure (38 +/- 3 versus 69 +/- 7 mm Hg) and coronary flow (46 +/- 2 versus 82 +/- 11 mL/min). In addition, ultrastructural morphology was preserved but only with in vivo pretreatment. Liver protein content was not increased in rabbits treated from 12 hours to 5 days with HIT versus controls, belying a protein neosynthesis mechanism. However, the temporal sequences suggested conversion of an inactive HIT profactor to an active form. CONCLUSIONS: Administration of serum derived from hibernating black bears to rabbits affords protection against ischemia-reperfusion injury compared with vehicle (saline)-treated animals in a rabbit isolated heart preparation. It is apparent that HIT deserves further identification and mechanistic study in the setting of ischemia-reperfusion injury.

Animals↗