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[Thyroid hormone levels in the peripheral blood of the ground squirrel Citellus parryi during winter hibernation].

In the Arctic ground squirrel Citellus parryi, thyroxine and triiodothyronine concentrations in the peripheral blood have been determined by RIA in various seasons and during a short hibernation period. It was shown that during hibernation (December-February), hormonal concentration is higher than during homoiothermal period (August-October). The highest concentration of the thyroid hormones was found in hibernating animals in January. The data obtained indicate that thyroid hormones are involved in control of hibernation of the species investigated.

Animals↗

Modulation of activity of the striatal dopaminergic system during the hibernation cycle.

To evaluate how the activity of a well-established neurotransmitter pathway is modulated by a behavioral state, 3H-spiperone binding sites and dopamine (DA) and DA metabolite concentrations were measured in the striata of ground squirrels in 5 phases of the hibernation cycle. Whereas levels of striatal DA and its deaminated metabolite DOPAC did not change significantly, the concentrations of the O-methylated-deaminated metabolite, homovanillic acid (HVA), decreased in all phases of hibernation relative to euthermia. Striatal 3H-spiperone binding sites declined across the hibernation cycle in parallel with the reduction of HVA concentration; receptor binding affinity was unchanged by arousal state. In conjunction with previously reported findings, these results are consistent with the hypothesis that hibernation is associated with a down-regulation of the postsynaptic D2 receptors secondary to increased extracellular DA concentration and reduced DA degradation.

3,4-Dihydroxyphenylacetic Acid↗

[Secretion of antidiuretic hormone and renal function during the awakening of Jaculus orientalis from hibernation].

Chemical analysis of kidney tissue from jerboa (Jaculus orientalis) during hibernation shows that the cortico-papillary gradient of Na+ ions is strongly reduced, whereas that of urea is completely suppressed. During the spontaneous rise in body temperature which occurs as the animal comes out of hibernation, the accumulation of Na+ in the papilla then in the medullary zones begins to increase from 25-30 degrees C body temperature, before the appearance of a urea gradient. This confirms the hypothesis that urea accumulation in the kidney medulla is coupled to active transport of sodium. This active transport may be partially dependent upon circulating ADH, circulating levels of which increase with increasing body temperature. Glomerular filtration in normothermic jaculus orientalis is 696 +/- 155 microliter . min-1 and urinary flow is relatively low in this desert species at 1.12 +/- 0.18 microliter . min-1. During hibernation at a body temperature between 7 and 8 degrees C glomerular filtration and urinary flow are not measurable. Glomerular filtration appears (51 microliter . min-1 at 26 degrees C) and increases at a temperature range where systemic blood pressure has already attained a normal level. This indicates that the reestablishment of glomerular filtration may be linked to intra-renal vasomotor events as is suggested by measurement of plasma renin activity during the coming out of hibernation.

Animals↗

[Ultrastructural changes in the renal filtration barrier during hibernation of the common dormouse (Eliomys quercinus L.)].

We have studied kidney samples of 16 garden dormouses (Eliomys quercinus L.) divided into two groups, 8 hibernating and 8 non-hibernating. Hibernation produces structural modifications in the glomerular ultrafilter: (1) the endothelial pores decrease in number and size; (2) the podocytic food processes increase in number and the slit pores decrease in size; (3) in the basement membrane there are no structural morphological modifications. In short, we could say that the permeability of the glomerular ultrafilter decreases during hibernation. This fact helps to understand the decrease in the rate of urine formation that takes place in the presence of a low body temperature and a metabolic depression.

Animals↗

Studies on Japanese encephalitis virus infection of reptiles. II. Role of lizards on hibernation of Japanese encephalitis virus.

A series of experiments on the role of lizards as overwintering hosts of Japanese encephalitis virus (JEV) was carried out. Two species of lizards, T. tachydromoides and E. latiscutatus, 2 species of mosquitoes, Cx. p. fatigans and Cx. p. pallens, and 2 strains of JEV, JaGAr#01 and JaGAr 19461, were used in this study. Firstly transmission of JEV from infected mosquitoes to uninfected lizards and from infected lizards to normal mice by the bite of mosquitoes was demonstrated successfully. Cx. pipiens group mosquitoes were found to feed readily on lizards as compared to Cx. tritaeniorhynchus, the primary vector of JEV in Japan. Secondly simulated hibernation of JEV in lizards was carried out under indoor and outdoor conditions. In the outdoor hibernation, lizards were injected with JEV on October 14, 1968, entered in hibernation on October 19 and were recovered from hibernation on April 10, 1969. Viremias were demonstrated in the lizards for a few weeks in late April. Thirdly JEV isolation and HI antibody detection were attempted from blood samples of field-caught reptiles, 7 species of snakes and 3 species of lizards and among amphibians, 2 species of frogs. HI antibody against JEV was found at a rate of 14.3% from E. latiscutatus and 4.0% from T. tachydromoides, though JEV was not isolated from all the blood samples of these cold-blooded animals. The roles of lizards as overwintering hosts of JEV were discussed.

Animals↗

[Changes in K+ transport in the liver mitochondria of gophers in hibernation].

Liver mitochondria of awake and hibernating squirrels maintain the same amount of K+ due to a decrease of K+-permeability during hibernation. The rates of DNP-stimulated K+-efflux and respiration-dependent K+-influx in mitochondria are diminished during hibernation. A two-fold increasing of K+-content and activation of K+-transport are observed at the arousing. Variations of K+-transport in mitochondria correspond to the changes in the channel-formed activity of K+-transporting protein isolated from the liver of this animals. This activity is maximal during arousal and is least during hibernation.

Animals↗

Protein and fat metabolism in hibernating bears.

Hibernation in the bear (Ursus americanus) is unique in that it is continuous for 3 to 7 months and occurs at near normal body temperature, yet the bear does not eat, drink, urinate, or defecate. During hibernation there is no loss of lean body mass because amino acids enter protein synthetic pathways at increased rates producing reciprocal decreases in entry into the urea cycle. The urea that is formed is hydrolyzed and the nitrogen released is combined with glycerol to form amino acids, which reenter protein synthetic pathways. Body fat supplies the substrate for metabolism (400 kilocalories/day). Ketosis does not occur. Metabolic water is sufficient to maintain normal hydration. About 100 ml of urine is filtered daily by the kidneys but the baldder wall transports water and solute back into blood at a rate about equal to their entry into the bladder. The bear cannot duplicate its winter adaptation in summer when housed in the cold and dark. During hibernation the bear shows hypothalamic hypothyroidism and increased testosterone production. These changes appear necessary for developing the selective states of anabolism and catabolism found in the hibernating bear.

Animals↗

The role of membrane fatty acids in mammalian hibernation.

During mammalian hibernation, cellular membranes continue to function at temperatures approaching 0 C. The molecular mechanisms that confer this capacity to the membranes are unknown but may be related to the fluidity of the membrane and to the level of unsaturated fatty acids. The basic tenets of membrane fluidity and the contribution of cholesterol, polar head groups, and fatty acids toward maintaining a fluid membrane in a liquid-crystalline state are examined in this review. It is shown that although unsaturated fatty acids can enhance membrane fluidity at low temperatures, there does not appear to be a consistent trend toward increased levels of unsatruated fatty acids during hibernation in all tissues of hibernators. Consequently, there may be some other role for the alterations in the composition of membrane fatty acids found during the hibernating cycle other than increasing membrane fluidity to permit continued activity at reduced temperatures.

Animals↗

[Glutaminase and glutamate decarboxylase activity of brain tissue during hypothermia and hibernation].

A forced cooling of rats and gophers decreases the brain glutaminase activity activated with phosphate with the incubation temperature. The cooling of rats leads to a decrease in the brain glutamate decarboxylase activity. However in the animals cooled down to 20 degrees C the incubation temperature (25 and 20 degrees C) does not affect it. The beginning of hibernation is accompanied by an increase in glutamate decarboxylase activity of the brain, a month later it lowers as compared with the hibernation beginning. The glutaminase activity falls during hibernation. At the hibernation beginning the activating effect of phosphate on the brain glutaminase is reduced, a week later it is intensified and by the end of a month period it is decreased again.

Animals↗

[Incorporation of labeled 3H-leucine in the acidic protein of the brains of hibernating animals].

3H-leucine was injected intraperitoneally to hibernating and awakening sousliks and to those being conscious for one or two weeks. Water-soluble brain protein extracts were separated by disc electrophoresis to determine relative radioactivity of the most acidic fraction which, under similar conditions, corresponds to the nerve-specific protein S-100. It was shown that in the brain cortex and reticular formation, the incorporation of the acidic protein drastically increases on awakening and reaches the maximum value on the 7th day. The high level of 3H-leucine incorporation into the hippocampus of the hibernating animals does not substantially change during the egress from hibernation. This may be related to the fact that during hibernation the hippocampus retains electrical activity.

Animals↗

[The temporal characteristics of "winter" paradoxical sleep in the hibernating suslik Citellus major].

It has been shown that paradoxical sleep (PS) total time (TT) in euthermia phase of hibernation cycle (winter sleep) can be compared with its mean values in euthermia season. Ultradian fluctuations of PS episodes duration, TT and phase number as well as bradycardia microintervals are revealed in euthermia phase dynamics. Amplitude of these fluctuations increases before hibernation entry; in transitional "start" period PSTT increases up to maximum critical values. In hibernation cycle PSTT rapidly decreases at the first stage owing to reduction of PS phase number and their duration. These data support and supplement earlier suggested hypothesis about endogenous "swinging up" of ultradian rhythms of sleep and thermoregulation promoting stage-to-stage expansion of homeostasis temperature limits in various critical periods of preparation and entry of homeotherms into natural hypometabolic states (torpor, hibernation and others).

Animals↗

The bladder wall under extreme stress condition: ultrastructural observations in a hibernating mammal.

Comparative ultrastructural observations are presented of the distended bladder of a hibernating dormouse (Muscardinus avellanarius) and a relaxed organ taken from an active animal. The distended bladder of the hibernating animal has an extremely thin wall lined with a three-layer urothelium. An osmiophilic coat lines the luminal surface of the urothelium in the hibernating animal, but it is very thin indeed in the specimen from the active dormouse. In the urothelium of the distended bladder, a larger number of fusiform vesicles (FVs, typical structures of the urothelium with asymmetric unit membrane) is found. On the contrary, lysosomes, multivesicular bodies, and interdigitation of plasma membrane between adjacent cells are all more frequent in the relaxed bladder of the active dormouse. Results suggest that hibernating animals can be a useful model for investigating the biology of epithelial cells in the mammalian bladder.

Animals↗

In vivo and in vitro effects of metabolic hormones on tissue respiration in toad, Bufo melanostictus during hibernation and active phase.

In vivo and in vitro effects of L-T3, L-T4, estradiol, corticosterone, epinephrine and norepinephrine were studied on the rate of liver and muscle tissue respiration in B. melanostictus during hibernation and active phase under natural climatic conditions. Thyroid hormones were found to be calorigenic only during the active phase. Estradiol stimulated the respiratory rate directly during hibernation and indirectly during the active phase. Adrenal hormones invariably increased the respiratory rate of the tissues in all the experiments. On the basis of the present findings it can be concluded that the sensitivity of the tissues to various hormones is altered during the active phase and hibernation. The calorigenic action of thyroid hormones seems to be associated with activity-linked energy demand. Direct stimulation of tissue respiration by estradiol during hibernation may be of great adaptative significance. Due to their temperature-independent calorigenic action, adrenal hormones may be considered as emergency hormones for the regulation of the oxidative metabolism in the toad.

Animals↗

The effects of hibernation on cone visual cells in the ground squirrel.

The cone visual cells of active, hibernating, and aroused 13-line ground squirrels have been studied by microscopy and autoradiography. Major changes occur throughout the cells during hibernation. The outer segments are shortened, and the diameters of the membranous discs may be reduced. Mitochondria are diminished in size and number, ribosomes are depleted, and the Golgi complex is fragmented into vesicles. Calycal processes are thickened, and synaptic ribbons become aggregated ectopically within the synaptic body. When hibernation is terminated, the cells recover rapidly. First, the basic synthetic machinery (mitochondria, ribosomes, Golgi complex) is regenerated,, and then the outer segments are repaired. This process is completed within 1 week. Many of the structural changes observed during hibernation are interpreted as effects of a temporary metabolic imbalance in which degradative mechanisms, including autophagy, are emphasized. In contrast, recovery is achieved by a comparable imbalance in which there is a transient accentuation of formative mechanisms. The recovered cells thereafter maintain a steady state of continuous self-renewal, in which formation and degradation are in balance.

Animals↗

The kinetic characteristics of the L-type calcium channels in cardiocytes of hibernators. 1. Development of a kinetic model.

The present paper described the experimental and theoretical investigations of the kinetic characteristics of the L-type Ca2+ channels in ground squirrels Citellus undulatus in two different physiological states (hibernation and spontaneous arousal). The perforated patch-clamp method was used in the experiments. It is shown that the potential-dependent Ca2+ current in isolated cardiocytes from hibernating animals is strongly inhibited during hibernation. An attempt was made to describe the kinetics of Ca2+ currents by the modified Hodgkin-Huxley equations. The experimental current traces are compared to the nonstationary solutions of the modified model, and the model parameters were found by optimization methods. It is shown that the simple dmfn model, where d is activation, f is inactivation, can not be used to describe the experimental characteristics at any power values m and n. Analysis of other models based on the conception of independence of activation and inactivation processes showed that in both physiological states-hibernation and spontaneous arousal-Ca2+ current was described by the model d2f1(2)f2, where d is activation, f1 and f2 are slow (f1-type) and fast (f2-type) inactivations of the channel.

Animals↗

The role of glucose metabolism in a pig heart model of short-term hibernation.

Previously, we reported, alterations in glucose metabolism in a 4 day model of chronic coronary stenosis similar to those described in patients with hibernating hearts. The purpose of this study was 2 fold: (1) to identify whether an acute model of mild, sustained ischemia could effect similar changes, and (2) to determine the effects of pharmacological inhibition of glycolysis. In the first group, extracorporeally perfused, intact pig hearts were subjected to 85 min of a 40% reduction in left anterior descending (LAD) coronary arterial blood flow. A second group was subjected to the same protocol, except after 40 min of LAD regional ischemia, iodoacetate (IAA) was administered to block glycolysis. Ischemia reduced MVO2 by 10% in both groups with a further 20% reduction noted following IAA treatment. Regional systolic shortening was reduced nearly 50% by ischemia and decreased an additional 40% following treatment with IAA. Glycolysis was increased by over 700% with ischemia in the first group. IAA caused a 3 fold reduction in glycolysis as compared to the preceding ischemic period and inhibited lactate production. Fatty acid metabolism was significantly reduced by ischemia in the first group, but was not reduced in the IAA group. Activity of creatine kinase associated with myofibrils was reduced and may have contributed to the contractile dysfunction. In conclusion, this acute model of short-term hibernation demonstrates several metabolic changes previously reported in chronic hibernation and may prove useful in determining mechanisms of substrate utilization in simulated conditions of chronic coronary stenosis and hibernation.

Animals↗

Heat shock protein changes in hibernation: a similarity with heart failure?

Myocardial hibernation is an adaptive phenomenon occurring during ischaemia. Patients with hibernating myocardium often have a history of an acute ischaemic insult, followed by prolonged hypoperfusion and symptoms of congestive heart failure (CHF), which is a complex syndrome involving several adaptational mechanisms. We tested the hypothesis that these two conditions evoke the myocardial expression of heat shock protein 72 (hsp72) as an adaptive response at the molecular level. Short-term acute hibernation was induced in isolated and perfused rat hearts subjected to 8 min total ischaemia followed by 292 min low-flow ischaemia (coronary flow: 1.0 ml/min), followed by 60 min of reperfusion. Total ischaemia caused quiescience. Subsequent low-flow resulted in a temporal early increase of lactate release, no re-establishment of developed pressure, no increase in diastolic pressure. Reperfusion resulted in 85.7 +/- 7.2% recovery of developed pressure, a small washout of lactate and CPK, no contracture, confirming that viability was maintained despite prolonged hypoperfusion. This sequence of events was linked to an increase in hsp72 content in the right (from 18.1 +/- 3.8% to 34.6 +/- 2.3%. P < 0.01) and left (from 19.7 +/- 2.6% to 37.6 +/- 3.3%, P < 0.01) ventricles. Three-hundred min of low-flow perfusion of the rat heart in absence of the short period of total ischaemia caused irreversible damage and failed to induced hsp72. CHF was induced in rats by intraperitoneal administration of monocrotaline. As a result, right ventricular weight increased from 171.3 +/- 7.2 to 412.3 +/- 18.7 mg. P < 0.001, peripheral and pleural effusion were evident and measurable, plasma arterial natriuretic peptide increased from 15.2 +/- 1.9 to 123.5 +/- 5.4 pg/ml, P < 0.001, confirming the occurrence of the syndrome of CHF. This was concomitant with significant expression of hsp72, more evident in the right (from 5.0 +/- 0.9% to 39.4 +/- 1.6%, P < 0.001) than in the left (from 3.5 +/- 0.6% to 13.0 +/- 1.2%, P < 0.001) ventricle. These data suggest that an adaptational process occurs at myocardial level during either hibernation or CHF. The expression of hsp72 could be viewed as a stereotyped adaptational reaction of the cardiac cell to stress conditions.

Animals↗

Quantification of cardioprotective gene expression in porcine short-term hibernating myocardium.

Several cardioprotective proteins are induced during myocardial ischemia, such as heat shock proteins and anti-apoptotic Bcl-2-related proteins which, when experimentally overexpressed, have been shown to prevent ischemia-induced myocyte loss. As this pathophysiological induction is obviously not sufficient to prevent losses of myocytes, we analysed whether it could occur under moderate myocardial ischemia with hibernation, thus potentially contributing to myocyte protection under these conditions. Therefore, using anesthetized pigs with documented myocardial hypoperfusion and short-term hibernation, we investigated the left ventricular mRNA expression of the inducible heat shock protein Hsp70 and of the anti-apoptotic Bcl-XL in comparison with the pro-apoptotic Bak and Fas expression. For transcriptional analyses, the porcine cDNA sequences of Bcl-XL, Bak and Fas were identified by polymerase chain reaction (PCR) or by screening of a porcine heart cDNA library and cloned. Using reverse transcription polymerase chain reaction (RT-PCR), we observed an unchanged mRNA expression of inducible Hsp70, Bcl-XL, Bak and Fas after 85 min of hypoperfusion in the short-term hibernating myocardium, as well as after 30 min of subsequent reperfusion in the stunned myocardium, compared with transcription in a non-hypoperfused control area of the same ventricle. In conclusion, the mRNA expression of inducible Hsp70 and of several apoptosis-modulating proteins is not altered during moderate myocardial ischemia resulting in short-term hibernation of the affected area and during subsequent stunning.

Amino Acid Sequence↗