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[Seasonal changes of the activity of calcium-transporting systems in the heart and skeletal muscles of hibernating animals].

In a short review of literature and according to our own data the molecular mechanisms providing seasonal adjustments of the activity of membrane Ca-transporting systems (Ca-channels and Ca-pumps) in muscle tissues of animals which spent winter time in a deep torpor state (hibernation), were analyzed. Special attention was paid to changes of protein composition of sarcoplasmic reticulum membranes--the key intracellular structure responsible for excitation-contraction coupling in different types of muscles, as well as to participation of endogenous protein kinases in regulation of functional activity of plasma membrane Ca-channels and sarcoplasmic reticulum Ca-ATPase during hibernation.

Animals↗

[Effect of artificial hibernation state on intensity of metabolic processes in rabbits].

Metabolic processes were investigated in the rabbit organism when modeling a condition of hibernation. It is established that during hibernation respiratory subcompensated acidosis develops in animals; the content of lactate and glutamate rises in their blood; activity of lactate dehydrogenase, malate dehydrogenase and isocytrate dehydrogenase increases in the liver cytosol of rabbits, while activity of pyruvate carboxylase and aldehyde dehydrogenase is reduced.

Acid-Base Equilibrium↗

[Participation of the ATP/ADP antiporter and fatty acids in oxidative phosphorylation uncoupling in squirrel liver mitochondria during winter hibernation and awakening].

The parameters of energy coupling of mitochondria isolated from the livers of hibernating and awakening gophers were studied. The ATP/ADP-antiporter inhibitor carboxyatractylate slowed down the respiration rate, increased delta psi and decreased the ionic conductivity of the inner mitochondrial membrane as measured by the rate of the delta psi decline after addition of cyanide (in the presence of oligomycin and EGTA). A similar effect was produced by BSA, carboxyatractylate being fairly ineffective in the presence of BSA. In hibernating gophers the maximal rate of the uncoupled respiration and the ionic conductivity of the inner mitochondrial membrane were markedly decreased as compared with awakening gophers. The data obtained suggest that in awakening animals fatty acids induce the uncoupling of oxidative phosphorylation by the ATP/ADP-antiporter, this process being simultaneous with the activation of the respiratory chain.

Animals↗

[Influence of spontaneous arousal during hibernation of the activity of the pituitary-adrenal system in the suslik Citellus erythrogenis].

Periodic spontaneous arousals of ground squirrels during hibernation are accompanied by activation of the hypophyseal-adrenal system. However, together with a 3-fold increase in hypophyseal ACTH and 2-fold increase in 11-oxycorticosterioid secretion by the adrenals, more than 2-fold decrease in the content of these hormones in the peripheral blood was observed. The latter may result from the increased corticosteroid metabolism. It is suggested that spontaneous arousals may act as a synchronizer of endogenous rhythm of the activity of the hypophyseal-adrenal system during winter hibernation.

11-Hydroxycorticosteroids↗

[A comparative neurophysiological analysis of thermoregulatory muscle activity in hibernating and nonhibernating animals during the development of hypothermia].

Comparative neurophysiological analysis of the motor units (MU) activity during hypothermia performed in ground-squirrels and rats, revealed a tendency of the MU firing rate to decrease whereas electromyographical patterns of thermoregulatory activity were found to be common both for hibernating and non-hibernating animals. The MU activity ceased in rats at their body temperature of 20-22 degrees C in contrast to 9-5 degrees C in ground-squirrels. Differences in thermoregulatory muscle tone distribution over muscle groups were found between those two species. Some mechanisms of neural regulation of cold shivering and of thermoregulatory muscle tone, are discussed.

Animals↗

[Hypothermic effect on mice of a 1-10 kD fraction of the small intestine of the hibernating suslik Citellus undulatus during hypoxia and hypercapnia].

Studies have been made on a possibility of inducing a prolonged hypothermia by injections to albino mice of a fraction with a molecular mass 1-10 KD isolated from the small intestine of hibernating ground squirrels. Specific conditions for the onset of hibernation (hypoxia, hypercapnia, temperature) were simulated. Exposure of mice to hypoxia and hypercapnia for 2 hours in combination with injection of the mentioned fraction extended hypothermic condition in animals up to 24-36 hours as compared to 2-3 hours after sole injection of the fraction. After the injection of 5-OT under the same conditions, the prolonged hypothermia was less stable.

Animals↗

[Role of the nonspecific modification of erythrocyte membrane lipids during hibernation in the suslik Citellus parryi].

Studies have been made on the content of cholesterol, phospholipids, fatty acid composition, the intensity of lipid peroxidation, the activity of Na+, K+-ATPase, as well as on the peroxide hemolysis in the erythrocytes in prehibernating and hibernating ground squirrels. Changes in partial content of cholesterol and in fatty acid composition of membranes are presumably due to the excessive lipid peroxidation during hibernation resulting from the decrease in the activity of antioxidative enzymes, which also accounts for the increase in peroxide hemolysis of erythrocytes.

Animals↗

Experimental rabies in hibernator rodents.

Experiments carried out in different seasons with different strains of rabies virus have shown that hibernation prolonged the incubation period in sousliks (Citellus major Pall.). Mean survival of the animals infected during the active period was 32 days, while during hibernation it was 147.3 days (P less than 0.05), in some cases up to 251 days. The virus was isolated from and/or detected by fluorescent antibody test in 50% of cases in the brown fat and in some cases in the salivary glands and visceral organs. The brown fat biopsy allowed to detect the virus not earlier than 6 days before death. We propose to use heterothermal rodents for the study of mechanism of rabies virus persistence and suggest that these animals might represent a natural reservoir for rabies.

Animals↗

[The role of the heart in rewarming the body of hibernating animals upon arousal].

The heart of ground squirrels is covered by a large amount of brown adipose tissue during the whole period of hibernation. During arousal and rewarming of heterothermal rodents, the highest temperature is detected in the brown adipose tissue and in the heart. During hibernation the heart rate is 10-12/min. On arousal, beginning from the early stage when the heart temperature is still low, a significant increase in the heart rate occurs followed by acceleration of the body rewarming of heterothermal animals.

Adipose Tissue, Brown↗

[Regulation of endocrine pancreas secretions (insulin and glucagon) during the periodic lethargy-waking cycle of the hibernating mammal].

In winter, hibernating mammals enter a long phase of lethargy which is characterized by low body temperature, depressed metabolism and minimal release of metabolic substrates from endogenous fuel stores. Periodically, they spontaneously warm themselves to regain the euthermic state. These arousals are, by contrast, times of high release and consumption of endogenous substrates. Insulin and glucagon may contribute to the control of both contrasting metabolic periods. The secretion and metabolic effects of these two hormones were investigated in two hibernators: the hedgehog (Erinaceus europaeus) and the edible dormouse (Glis glis). During lethargy, blood glucose, insulin and glucagon concentrations were low. In vivo and in vitro studies showed that the secretion of both hormones was markedly depressed by low temperatures. Insulin secretion was not stimulated by glucose, although glucagon secretion remained reactive to arginine. Blood glucose was not regulated by insulin but pharmacological doses of glucagon increased blood glucose concentrations. The tissues were found to be highly insulin-resistant, preventing the fall of blood glucose and consequently limiting the depletion of glucidic substrates during the long periods of starvation. During arousal, blood glucose, insulin and glucagon levels increased at the end of rewarming while glucose turnover gradually increased above a body temperature of 15 degrees C. The effects of glucagon and insulin on glucose metabolism increased markedly beyond this stage. Thus the metabolic effect of both hormones are temperature-dependent. Insulin and glucagon allow an increase in glucose availability for the active metabolic processes which occur during arousal.

Animals↗

[Functioning of the sorbitol pathway of glucose metabolism during hibernation].

Studies have been made on the activity of sorbitol dehydrogenase and glucose-6-phosphate dehydrogenase in the liver of hibernating ground squirrels. It was found that the activity of the former is an order higher than that of the latter. Contribution of sorbitol pathway in total metabolism of the glucose in hibernating ground squirrels is discussed.

Animals↗

[Morphological behavior of the renal corpuscle of the garden dormouse during hibernation].

We studied 20 garden dormouses (Eliomys quercinus), 10 of which had hibernated. The renal tissue was fixed in Bouin's fluid, embedded in paraffin and sectioned at 7 microns; the sections were stained with azocarmin. These preparations were studied with an optical microscope (Leitz SM-Lux). Hibernation causes an increase in the corpuscular, glomerular and Bowman capsular areas. We thought that this statistically significant increase in the size of the corpuscular structures might be due to the glomerular blood stasis and larger flow of plasma ultrafiltrated towards the capsular space, because of an intense vasoconstriction of the efferent arteriole; this vasoconstriction is due to sympathetic stimulation and renin hypersecretion.

Animals↗

[Ultrastructure of parietal cells in summer and in the period of hibernation].

The parietal cells of active and hibernating citellus erythkogenus Br. were studied by electron microscopy and morphometric analysis. It was shown that there are clear-cut changes in the ultrastructure of parietal cells during hibernation, which reflect the absence of secretory activity of the cells. No pronounced dystrophic changes in morphology of the parietal cells were found. Structural differences due to the life stages of the cells were preserved.

Animals↗

[Changes in thermoregulation in the white mouse treated with endogenous substances from the intestinal tissue of hibernating animals].

Intraperitoneal administration of extracts of the small intestine epithelium of hibernating ground squirrels (C. Parryi Rich., C. undulatus) to white mice caused a decrease in oxygen consumption by 50-80%, the 5.5-14.0 degrees C drop in body temperature, inhibition of the muscle shivering thermogenesis, a decrease in heart rate, reduction of locomotor activity, development of hypnogenic effect and a closer dependence of body temperature on environmental fluctuations. The effects lasted for 30-40 hrs. Extracts from the small intestine tissue of non-hibernating ground squirrels caused insignificant changes of these parameters.

Animals↗

[Changes in the wakefulness-sleep cycle in mice induced by endogenous substances from the tissues of the susliks Citellus parryi and C. undulatus during hibernation].

Intraabdominal injections of albino mice of extracts from the brain (2mg/g) and epithelial tissue of the small intestine (1.3 mg/g) of hibernating ground squirrels result within 6 hours in the decrease of the duration of the awake state (by 2.1-2.4 times), inhibition of paradoxical sleep, the increase in the duration of the slow wave sleep, and the decrease in the brain temperature (by 4.5-6 degrees). These indices are affected to a significantly lower extent by injections of intestinal extracts from non-hibernating animals. It is suggested that in homoiothermic animals, changes of temperature homeostasis and sleep cycle are controlled by endogeneous substances which are present in the brain and tissues of the internal organs.

Animals↗

[Glycogen content and phosphorylase activity in various muscles of rats and gophers during hypothermia, metabolic heating and hibernation].

Hypothermia (30 and 20 degrees C) of rats and gophers did not decrease the level of glycogen and did not change the activity of phosphorylase in musculus masseter, musculus gastrocnemius, musculus soleus. In musculus trapezius of rats the content of glycogen decreased by 34.5% under cooling down to 30 degrees and by 59.5% under cooling down to 20 degrees. A fall in muscular glycogen was observed under self-heating of rats and gophers after 20 degrees hypothermia and especially in awakening from hibernation. The portion of phosphorylase a increased in muscular tissues of gophers during a three-month hibernation (10-12 degrees) and awakening.

Animals↗

[Acidic protein content in the brain structures of hibernating animals].

The water-soluble protein extracts from the different brain structures of hibernating animals were separated by means of disc-electrophoresis in polyacrylamide gel. The relative content of the most acidic protein corresponding to the nerve-specific protein S-100 under the same experimental conditions was determined in various physiological states. It is shown that the quantity of this protein in the brain stem increased in awakening animals as compared to the hibernating ones whereas its content in the cortex and hippocampus was stable.

Animals↗

[Biologically active peptides isolated from the brain of hibernating ground squirrels].

More than 20 peptides have been isolated and sequenced from the brain of hibernating ground squirrel Citellus undulatus. Some of the isolated peptides were chemically synthesized and investigated for the spectrum of biological activity. One of the isolated peptides, neokyotorphin (Thr-Ser-Lys-Tyr-Arg), earlier known as a weak analgetic, is found to have a cardiotropic and thermoregulatory activity. Neokyotorphin activates in vitro voltage-dependent calcium and blocks ATP-dependent potassium currents in the frog atrial fibres. Intraperitoneal injection of this peptide in hibernating ground squirrels speeds up the arousal of animals increasing sharply the heart rate and oxygen consumption. Intraperitoneal and intranasal administrations of neokyotorphin in rats raises body temperature in thermoneutral conditions (26-28 degrees C) exerting no effects at low (4-6 degrees C) and high (31-32 degrees C) environmental temperatures. Another isolated peptide, Asp-Tyr, blocks the inward voltage-dependent calcium current in the frog atrial fibres and slightly increases the outward potassium current. Sulfated analogue of this dipeptide (aspartyl-O-sulfate-tyrosine) more effectively blocks the inward voltage-dependent calcium current in the frog atrial fibres and have no effects on the outward potassium current.

Amino Acid Sequence↗