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Rapid temperature changes induce adenosine-mediated depression of synaptic transmission in hippocampal slices from rats (non-hibernators) but not in slices from golden hamsters (hibernators).

Disturbances in neuronal communication induced by rapid temperature changes are a risk in the context of accidental hypothermia and would be fatal for hibernators during arousal from hibernation. Therefore, we investigated the effects of rapid temperature changes on synaptically induced CA1 population spikes in hippocampal slices from golden hamsters (hibernators) and rats (non-hibernators). Temperature was changed ramp-like by 0.3 degrees C/min, which corresponds to the rise of body temperature in golden hamsters during arousal from hibernation. During cooling from 35 to 10-15 degrees C, the population spike amplitude increased, reached maximal values at 25-30 degrees C and 20-25 degrees C in hamster and rat slices, respectively, and then decreased with further cooling. During rewarming, hamster slices displayed the same temperature dependence as during cooling. In contrast, in rat slices dynamic effects of the temperature change occurred. These were most obvious in a strong depression of the spike amplitude during rewarming as compared to cooling. Above 26-29 degrees C, the depression was superimposed by an excitatory effect. The depression was largely attenuated by theophylline (100-200 microM) and thus seems to be based on an increase of the concentration of endogenous adenosine, which in turn may result from an imbalance in energy metabolism during warming. The lack of warming-related depression in hamster slices can be explained by a lower sensitivity for adenosine as compared to rat slices. In addition, a better resistance of metabolic balance against rapid temperature changes may prevent large elevations of endogenous adenosine in the hamster hippocampus. For hibernators, the avoidance of temperature change-induced disturbances of neuronal communication may be a prerequisite for safe arousal from hibernation.

Acclimatization↗

Resistance of erythrocytes of hibernating mammals to loss of potassium during hibernation and during cold storage.

In two species of hibernators, hamsters and ground squirrels, erythrocytes were collected by heart puncture and the K content of the cells of hibernating individuals was compared with that of awake individuals. The K concentration of hamsters did not decline significantly during each bout of hibernation (maximum period of 5 days) but in long-term bouts in ground squirrels (i.e. more than 5 days) the K concentration of cells dropped significantly. When ground squirrels were allowed to rewarm the K content of cells rose toward normal values within a few hours. Erythrocytes of both hamsters and ground squirrels lose K more slowly than those of guinea pigs (nonhibernators) when stored in vitro for up to 10 days at 5 degrees C. In ground squirrels the rate of loss of K during storage is the same as in vivo during hibernation, and stored cells taken from hibernating ground squirrels also lose K at the same rate. The rate of loss of K from guinea pig cells corresponded with that predicted from passive diffusion unopposed by transport. The actual rate of loss of K from ground squirrel cells was slower than such a predicted rate but corresponded with it when glucose was omitted from the storage medium or ouabain was added to it. Despite the slight loss of K that may occur in hibernation, therefore, the cells of hibernators are more cold adapted than those of a nonhibernating mammal, and this adaptation depends in part upon active transport.

Adaptation, Biological↗

The liver of Testudo graeca (Chelonia). A comparative study of hibernating and non-hibernating animals.

In the present work, a comparative study of the liver of hibernating and non-hibernating specimens of Testudo graeca (Chelonia) has been carried out by light and electron microscopy. During hibernation, the morphological changes which take place do not affect the general architecture of the liver, but are mainly concerned with the number and distribution of the cytoplasmic organelles and reserve materials in the hepatocytes. In non-hibernating animals, the cytoplasm of the hepatocytes has a large number of organelles indicating a high cell activity, as well as numerous lipid droplets and glycogen. In hibernating animals, the size of the hepatocytes is reduced and the cytoplasm is vacuolated. There is also an increase in lysosomal activity due to the increase in the number of secondary lysosomes in the cytoplasm. Sacs full of degenerating hepatocytes can be observed among the hepatic cells. Glycogen and lipid droplets are not present in the hibernating animals. The present study demonstrates that, during hibernation, the hepatocytes likely undergo ultrastructural changes related to the synthesis, storage and release of reserve material.

Animals↗

Effects of hibernation and arousal from hibernation on mesenteric arterial responses of the golden hamster.

The aim of our study was to investigate the changes that occur in functional responses of the golden hamster mesenteric arterial bed after: 1) 8 wk of hibernation and 2) 2 hr after arousal from hibernation. Age-matched and cold-exposed hamsters were used as controls. At 8 wk after hibernation there was an increase in sensitivity of vasoconstrictor responses to sympathetic nerve stimulation but no significant difference in constrictor responses to norepinephrine, alpha,beta-methylene ATP, uridine 5'-triphosphate or KCl (studied in unconstricted preparations), or in endothelium-dependent vasodilatation to acetylcholine and uridine 5'-triphosphate (in methoxamine-preconstricted preparations) compared with the control groups. In contrast, in the arousal from hibernation group, sympathetic vasoconstriction was similar to that in the control groups, and the maximal response to exogenous norepinephrine, and responses to alpha,beta-methylene ATP were augmented. These results suggest that there is an augmentation of sympathetic neurotransmission of golden hamster mesenteric arteries at 8 wk after hibernation, which appears to be due to pre- rather than postjunctional changes. This is reversed with arousal from hibernation, when the sensitivity of sympathetic contractile responses is not different from that of the controls. However, an increase in maximal constrictor responses to norepinephrine suggests that postjunctional changes may occur in sympathetic neurotransmission during arousal.

Acetylcholine↗

Morphine antinociception in the non-hibernating and hibernating states of the ground squirrel (Citellus lateralis).

Previous work in our laboratory demonstrated a significant reduction in the development of morphine physical dependence during hibernation, suggesting a major change in the ability of morphine to act on the central nervous system (CNS) during this naturally altered state. To further investigate the pharmacological actions of morphine during the hibernating (H) state, the present study recorded skin-twitch response (STR) latency as a measure of morphine antinociception in the golden-mantled ground squirrel (Citellus lateralis) during the non-hibernating (NH) and H states. Our results revealed that morphine antinociception continued to develop in hibernation. Moreover, the magnitude of antinociception displayed was greater during the H state than in the NH state. Tolerance to morphine's antinociceptive effects developed in both states as well. The results of the present study indicate that the hibernation-related reduction in the development of morphine dependence represents a selective, rather than a general, suppression of the CNS pharmacological actions of morphine during the H state.

Animals↗

The kidney during hibernation and arousal from hibernation. A natural model of organ preservation during cold ischaemia and reperfusion.

BACKGROUND: During hibernation the kidney is in a hypothermic condition where renal blood flow is minimal and urine production is much reduced. Periodical arousal from hibernation is associated with kidney reperfusion at increasing body temperature, and restored urine production rate. METHODS: To assess the degree of structural preservation during such extreme conditions, the kidney cortex was investigated by means of electron microscopy in the dormouse Muscardinus avellanarius during winter hibernation, arousal from hibernation and the summer active period. RESULTS: Results show that the fine structure of the kidney cortex is well preserved during hibernation. In the renal corpuscle, a sign of slight lesion was the focal presence of oedematous endothelial cells and/or podocytes. Proximal convoluted tubule cells showed fully preserved ultrastructure and polarity, and hypertrophic apical endocytic apparatus. Structural changes were associated with increased plasma electrolytes, creatinine and urea nitrogen, and proteinuria. During the process of arousal the fine structure of the kidney cortex was also well maintained. CONCLUSION: These results demonstrate that dormice are able to fully preserve kidney cortex structure under extreme conditions resembling e.g. severe ischaemia or hypothermic organ storage for transplantation, and reperfusion. Elucidation of the mechanisms involved in such a natural model of organ preservation could be relevant to human medicine.

Animals↗

Ultrastructure of the tubular nephron of Testudo graeca (Chelonia). A comparison between hibernating and non-hibernating animals.

The tubular nephron of hibernating and non-hibernating specimens of Testudo graeca (Chelonia) was studied by means of conventional light and electron microscopy and histochemistry. The tubular nephron was composed of proximal, intermediate, distal and collecting tubules in both hibernating and non-hibernating animals. The cells of the proximal tubule showed long microvilli, cytoplasmic vacuoles, a developed endoplasmic reticulum and abundant mitochondria. Fat droplets were also observed. The intermediate segment was lined by ciliated and non-ciliated cells. The lining cells of the distal tubule presented few microvilli, abundant dense mitochondria and clear vesicles of mucous appearance in the terminal portion. Collecting ducts are composed of mucous and non-mucous cells. Mucous cells presented strong reaction to the histochemical techniques detecting sialo- and sulpho-mucins. During hibernation, a progressive vacuolar degeneration of the endoplasmic reticulum was observed in all the segments of tubular nephron, which may be caused by a massive intake of extracellular water into the cell.

Animals↗

[Protein synthesis in cardiac cells and the ultrastructural dynamics of cardiomyocytes of hibernating animals during the hibernation cycle].

A significant increase in protein synthesis correlating with ultrastructural dynamics of cardiomyocyte organelle convertions has been demonstrated in cardiomyocytes of ground squirrel during arousal from hibernation. In hibernating ground squirrels, the ultrastructure of protein-synthesizing organelles and of the cardiomyocyte nucleus points out to the readiness of cells to active synthesis of proteins. In the perinuclear area of cardiomyocytes abundant ribosomes, elements of endoplasmic reticulum and Golgi complex, mitochondria and high-energy substrates--glycogen and lipid inclusions--are seen. The cardiomyocyte nuclei are large, with highly convoluted borders and abundant pores, their nucleolar structure is granular, the chromatin is mainly diffuse. The potency of cardiomyocyte protein-synthesizing system of hibernating ground squirrels is realized every time at periodical arousals during hibernation. The role of cyclic changes of protein synthesis rate in adaptation of cells of hibernating mammals to functioning at various temperatures is discussed.

Adaptation, Physiological↗

Is the polar bear (Ursus maritimus) a hibernator? Continued studies on opioids and hibernation.

Polar bear behavior and biochemistry suggest they may have the ability to hibernate year-round, even though this species is not considered to be a true hibernator. This observation, plus the discovery of a hibernation-induction trigger (HIT) in the blood of black bears, prompted the examination of polar bear blood collected throughout the year for evidence of HIT, and to determine if it displayed opioid activity, as black bear blood does. A bioassay was conducted by injecting summer 13-lined ground squirrels with serum collected from polar bears at different seasons. One group of squirrels was previously implanted with osmotic pumps containing naloxone. The rest had pumps containing saline. Squirrels with saline pumps all hibernated significantly more than those with naloxone, except the group receiving blood from a November polar bear, observed to be highly active and hyperphagic. An in vitro study, using guinea pig ileum, showed that 400 nM morphine inhibited induced contractions and 100 nM naloxone reversed the inhibition. Ten mg of winter polar bear serum albumin fraction (to which HIT binds in ground squirrels and woodchucks) had a similar inhibiting effect, but naloxone, even at 4,000 nM, didn't reverse it. It is concluded that polar bear blood contains HIT, that it has an inhibiting effect, but naloxone, even at 4,000 nM, didn't reverse it. It is concluded that polar bear blood contains HIT, that it has an opioid effect, but may not itself be an opioid.

Animals↗

Ultrastructure of the renal corpuscle of Testudo graeca (Chelonia). A comparison between hibernating and non-hibernating animals.

The renal corpuscle of hibernating and non-hibernating Testudo graeca was studied by means of light and electron microscopy. Renal corpuscles are small and have a glomerular architecture similar to that found in other vertebrates with a limited glomerular filtration rate. In hibernating animals, unlike non-hibernating, some morphological changes took place. The cells of the renal corpuscle were densely packed, podocytes and parietal cells showed a marked cytoplasmic vacuolization, there was a highly developed capillary basement membrane and the endothelial and mesangial cells showed abundant dense granules. These morphological features apparently correspond to a vacuolar degeneration. They may also be the morphological basis of the decrease in the glomerular filtration rate observed during this period.

Animals↗

Involvement of adrenal hormones in tissue respiration of sub-tropical hibernating and non-hibernating species of frogs.

Effects of norepinephrine (NE), epinephrine (EP), corticosterone and cortisol were studied both in vivo and in vitro on the rate of oxygen consumption of tissues (liver, skeletal muscle and kidney) of sub-tropical Indian frogs Rana limnocharis (a hibernating species) and Rana cyanophlyctis (a non-hibernating species) exposed to natural climatic conditions during winter and summer/rainy seasons. Further, the effects of NE and EP were also studied in vitro in the presence of specific beta- and alpha-adrenergic antagonists (propranolol and prazosin). NE, EP and corticosterone, when administered in vivo or in vitro, significantly stimulated the respiratory rate of the tissues of both the species irrespective of the seasons/temperature. Results suggest that NE, EP and corticosterone are directly involved in regulation of the energy metabolism of both hibernating and non-hibernating species of sub-tropical frogs. The calorigenic action of NE and EP seems to be mediated by both beta- and alpha-adrenergic receptors. However, the temporal involvement of beta- and alpha-adrenergic receptors seems to be tissue-dependent.

Adrenal Cortex Hormones↗

Norepinephrine release is increased in the hibernating heart, studied in a chronic canine model of myocardial hibernation.

We examined the change in cardiac sympathetic function in the hibernating heart. To induce hibernating hearts in dogs, we placed a nylon tube via the carotid artery in the left circumflex artery (LCx) and obstructed the LCx flow. The plasma norepinephrine (NE) and epinephrine (E) concentrations in the coronary sinus and the aorta were measured before and 1 week after the tube placement to evaluate the catecholamine release from the heart. The wall motion was followed by echocardiography and. 1 week after the tube placement, regional myocardial blood flow (RBF) was measured using colored microspheres. Also. the restorability of myocardial dysfunction was examined in other dogs by extracting the LCx tube 1 week after the placement. Finally, the heart was removed for pathological observation and dogs showing myocardial infarction were excluded. One week after placing the tube, wall thickening was reduced in the LCx area, but was not in the left anterior descending (LAD) area. Compared with the LAD area, RBF in the LCx area was decreased in the endocardium (p < 0.05), but was not in the epicardium. In other dogs, the reduced wall thickening in the LCx area was restored to normal levels 1 or 2 weeks after the tube extraction. Thereby, our dogs with the tube placed were considered to be models of myocardial hibernation. The plasma NE and E concentrations were not significantly changed by placing the tube, but NE release from the heart was increased after the tube placement (p < 0.05). E uptake from the heart did not differ. Therefore, it is suggested that NE release is increased in the hibernating heart and may contribute to its mechanism.

Animals↗

Thermosensitivity of preoptic neurones in a hibernator (golden hamster) and a non-hibernator (guinea pig).

Thermosensitivity of preoptic units was studied at hypothalamic temperatures (Thy) ranging from 8-43 degrees C in golden hamsters in a non-hibernating state as well as in guinea pigs. In golden hamsters 2 types of thermoresponsive preoptic neurones were found: 1. Neurones sensitive to Thy ranging from 10-42 degrees C with an exponential characteristic and very high spontaneous firing rates (29-59 imp/s) at Thy 36-37 degrees C. 2. Neurones with a bell-shaped temperature-firing rate characteristic, a negative temperature coefficient at Thy 40-30 degrees C, a maximal activity at Thy 20-30 degrees C and a positive temperature coefficient (+0.8 to +4 imp/s-degrees C) even at Thy close to 10 degees C. In guinea pigs thermoresponsive preoptic units became inactive or insensitive to thermal stimulation as soon as Thy fell below 30 degrees C. These results suggest that in hibernators central nervous structures involved in temperature regulation are adapted to maintain their function over the wide range of core temperatures which occur during the different phases of hibernation.

Animals↗

Sciatic nerve response to injury in hibernating and non-hibernating ground squirrels.

At 21 and 36 postcrush days, regenerating axonal sprouts were observed and counted in the distal stumps of sciatic nerves from non-hibernating ground squirrels (Tb = 37 degrees C). More importantly, regenerating axonal sprouts were present in the distal segments of sciatic nerves from hibernating ground squirrels (Tb = 4-10 degrees C), but the total number was significantly less than the number noted in non-hibernating animals.

Animals↗

Seasonal variations of DNA synthesis in intestinal epithelial cells of hibernating animals--I. DNA synthesis in intestinal epithelial cells of ground squirrel (Citellus undulatus) during deep hibernation.

The conditions for obtaining crypt cells from ground squirrel small intestine were chosen which allow flow-through cytofluorometric analysis of the DNA synthesis of this tissue. DNA synthesis was found to be greatly reduced in the intestinal crypt cells of ground squirrel during deep hibernation in torpid animals, in animals during spontaneous arousals and in animals prevented from hibernation. The conclusion is made about endogenous control of the DNA synthesis in the cells of true hibernators.

Acclimatization↗

Seasonal variations of DNA-synthesis in intestinal epithelial cells of hibernating animals--2. DNA-synthesis in intestinal epithelial cells of ground squirrel (Citellus undulatus) during autumn and late hibernation season.

1. DNA-synthesis was found to be gradually reduced in the intestinal crypt cells of ground squirrel during autumn at the time of preparation for hibernation and gradually rose during late hibernation season in February-March at the time of preparation for arousal. 2. A conclusion is made on the seasonal variations in cell replacement of true hibernators.

Animals↗

Hibernation triggers and cryogens: do they play a role in hibernation?

A survey of the literary evidence on cryogens and hibernation induction triggers is given and the results of experiments on the effect of hypothalamic or i.v. injections of opioids and plasma from hibernating European hamsters on body temperature control of rabbits are presented. Pharmacological doses of a delta opioid--DADLE (25 or 50 micrograms), when injected into the anterior hypothalamus, induce a small and short-lasting hypothermic effect in cold exposed rabbits, due to the downward shift of the temperature threshold for shivering. Lower doses (5 micrograms) are without effect, similarly as i.v. administrations (500 micrograms/kg) of this substance. Intrahypothalamic injections of met-enkephalin (0.1-1 microgram) induce a slight hyperthermia due to the shift of all thermoregulatory effectors to higher body temperatures. Intrahypothalamic injections of plasma from hibernating European hamsters do not influence the body temperature control in rabbits.

Animals↗

Prolongation of hibernation bout duration by continuous intracerebroventricular infusion of melatonin in hibernating ground squirrels.

Melatonin was infused intracerebroventricularly into hibernating golden-mantled ground squirrels (Citellus lateralis) maintained at 5 degrees C in darkness. Continuous infusion at a rate of 0.5 microliter/h was accomplished using an osmotic minipump. The effect of melatonin on hibernation bout duration was determined with reference to the natural trend in bout duration for each animal. At doses of 200 and 400 ng/h, melatonin produced a dose-related increase in bout duration. No effect was observed following control infusions of artificial cerebrospinal fluid or lower doses of melatonin.

Animals↗