Kyotorphin suppresses proliferation and Ca2+ signaling in brown preadipocytes.

A positive correlation was revealed between stimulation of protein and DNA synthesis in preadipocytes by norepinephrine or neokyotorphin and intracellular Ca2+ concentration in these cells. Kyotorphin abolished the stimulatory effect of norepinephrine on proliferation of cultured cells and cold-induced [3H]-thymidine incorporation into DNA of mouse brown adipose tissue in vivo. These changes correlated with peptide-induced suppression of slow calcium signaling in preadipocytes.

[The annual involution and regeneration of the thymus in hibernating animals and perspectives of its studies in gerontology and stem cell proliferation]. / Ezhegodnaia involiustiia i regeneratsiia timusa u zimnespiashchikh i perspektivy ee issledovanii v oblasti gerontologii i proliferatsii stvolovykh kletok.

Data on a unique phenomenon of annual involution and neogenesis of thymus gland in hibernating animals are reviewed. In accordance with morphological findings, the annual thymus involution in hibernating animals is close to the age-dependent thymus involution occurring in all mammals once in a lifetime. In opposite, thymus involution in hibernating animals is totally different from the accidental involution. During hibernation, the thymus tissue is substituted by the brown fat tissue. In the spring, thymus gland neogenesis stats with intensive growth of epithelial tissue followed by lymphocyte infiltration and exhaustion of brown tissue. Morphological changes in the thymus gland within the annual cycle were compared with seasonal dynamics of structural and functional changes in peripheral lymphoid organs (spleen, lymphoglandular, peritoneal fluid). A general regularity was observed involving a decreased functional activity of immune cells in autumn, its sharp depression during winter hibernation, and obvious increase in summer with the onset of a season of animal activity. It is supposed that a sharp increase in the tumor necrosis factor (TNF) production observed during short-term awakenings in winter may serve an important link in this unique immune adaptation mechanism. The season changes in cellular TNF secretion suggest a mobilization of protective resources in hibernating animals in autumn and winter, i.e. in seasons when the thymus gland activity is depressed. The annual involution of thymus gland cannot be related to droppings in the environmental or body temperatures, as it comes long before their fall. Additionally, it is not related to ageing, as it occurs already in young hibernating animals. The role of hormones, including melatonine and corticosteroids, in mechanisms regulating thymus gland involution in hibernating animals is discussed.

[Characteristics of force-frequency relations in the myocardium of the squirrel Citellus undulatus]. / Osobennosti ritmoinotropnykh otnoshenii v miokarde suslika Citellus undulatus.

The force-frequency relationship (FFR) in papillary muscles of the heart of active ground squirrel in different seasons was studied. For comparison, similar preparations from rat and rabbit were used. It was shown that the FFR of papillary muscles of active ground squirrel undergo significant seasonal changes. In summer and a part of autumn squirrels, a negative staircase (a decrease in the isometric force with increasing stimulation frequency) similar to that in adult rat was revealed. The FFR of the majority of autumn, winter and spring squirrels were polyphasic and contained both positive and negative components. Changes in the force in response to the introduction of pauses at a constant stimulation frequency were recorded. Two types of the post-rest recovery pattern were revealed in the myocardium of ground squirrels. For frequencies range with the negative direction of FFR, a typical pattern of rest-potentiation similar to that in rat papillary muscles was observed. The amplitude of the first post-rest contraction (F1) was usually higher than that of the preceding steady-state contraction. In papillary muscles of autumn animals the F1 value was greater that in summer, which suggests an enhanced release of Ca2+ from the sarcoplasmic reticulum. There was no post-rest potentiation in the range of frequencies with positive direction of FFR, and the post-rest recovery pattern in these cases was principally different from those of rat and rabbit preparations. It was proposed that seasonal differences of the FFR of active ground squirrel heart are associated with changes in the ratio of activities of the calcium-transporting system in the hibernation period.

[Seasonal changes in tumor necrosis factor production in hibernating animals in normal conditions and under the effects of electromagnetic and ionizing radiation]. / Sezonnye izmeneniia produktsii faktora nekroza opukholei u zimnespliatshchikh zhivotnykh v norme i pri deistvii élektromagnitnykh i ioniziruiushchikh izluchenii.

Production of tumor necrosis factor (TNF) has been investigated in peritoneal macrophages and splenic T cells of Arctic Yakutian ground squirrel (Citellus Undulatus Pallas) upon in vitro action of electromagnetic and ionizing radiation during annual cycle. The significant activation of TNF production in the cells of awaken ground squirrels in winter and increasing level of the lymphokine production at spring-summer period has been indicated. The level of TNF production in splenic T cells was not changed during whole year. The electromagnetic radiation (EMR) of low intensity (8.15-18 GHz, 1 microW/cm2) induced an augmentation of both secretory and proliferative activity in TNF-producing cells. Ionizing radiation suppressed T cell proliferation, but the doses 2 and 5 Gy resulted in a significant stimulation of TNF production in T cells and macrophages.

Seasonal peculiarities of behavior of ground squirrel Citellus undulatus in holeboard and open field tests.

Seasonal changes in the behavior of ground squirrels Citellus undulatus (n=35) in holeboard and open field tests were studied. It was found that the number of head dips and rearings in the holeboard and the number of crossed squares, rearings, and runs across the field center in the open field in ground squirrels during arousal between bouts at the end of the hibernation period, in the middle of March, were lower than these indices in active summer animals. A rapid restoration of all behavioral parameters after the arousal of animals from hibernation in mid-April was shown. In some cases, the behavioral parameters of activity in the holeboard and open field tests and the habituation reaction reached the values characteristic of active summer animals in a very short period of time, sometime within 1 day. By contrast, the locomotory and exploratory activities of animals tested in autumn (at the beginning of September and in the middle of October) were significantly lower than in summer animals, i.e. these indices decreased to minimum values 1.5-2 months prior to their entry into hibernation. The results of behavioral experiments indicate that the preparation of the CNS of hibernators for seasonal changes in the functional states is under the control of endogenous regulators.

Effects of L-thyrosyl - L-arginine (kyotorphin) on the behavior of rats and goldfish.

The effects of kyotorphin (KTP), a dipeptide (L-Tyr-L-Arg), on the level of sensory attention to stimuli of different modalities in rats and the exploratory behavior in goldfish were investigated. In both cases KTP was found to suppress the exploratory activity. When 5-HTP, a precursor of serotonin synthesis, is activated the inhibitory effects of KTP increased. It is assumed that the regulatory effect of KTP on the exploratory behavior of animals is mediated by the monoaminergic (neurotransmitting) brain systems, as distinct from its analgetic effects, which are mediated by the opioid brain systems.

[Seasonal characteristics of the monoaminergic regulation of the behavior of hibernating animals]. / Sezonnye osobennosti monoaminergicheskoi reguliatsii povedeniia giberniruiushchikh zhivotnykh.

The stimulating effect of L-DOPA on exploratory activity of the ground squirrel in the hole-board and open field experiments was stronger in the spring than in autumn, whereas the regulating effect of the 5-HTP on adaptive behaviour of hibernating animals was stronger in autumn. Results of the biochemical analysis of the MAO A activity with serotonin or noradrenaline as substrates revealed a seasonal dependence of the substrate specific changes of this enzyme activity in hibernating animals. The data obtained suggest that the seasonal distinctions in effects of similar pharmacological agents depend on activity of the brain monoaminergic systems' activity in hibernating animals in different periods of the annual cycle.

Production of tumor necrosis factor in cells of hibernating ground squirrels Citellus undulatus during annual cycle.

TNF production has been studied in peritoneal macrophages and splenic T cells of Arctic Yakutian ground squirrel (Citellus Undulatus Pallas) in hibernating and awake animals in winter and in prehibernating autumn as well as in active euthermic spring-summer animals. A high level of TNF production in macrophages of ground squirrel is observed over the active period and during arousals in winter. There are no significant season variations in TNF production in splenic T lymphocytes of ground squirrels. This suggests the major role of activated macrophages in the arousals of hibernating animals. T lymphocyte proliferation in ground squirrels in the active period is higher than in winter, and the most significant seasonal variations are found in T cell mitogenic response, which increases in spring-summer period. Evidence is presented that functional activity of macrophages of squirrel in autumn has much in common with that in winter rather than in spring-summer period.

[Effect of insulin on the myocardium of the active, hibernating and wakening ground squirrel Citellus undulatus]. / Vliianie insulina na miokard aktivnogo, giberniruiushchego i probyzhdaemogo suslika Citellus undulatus.

The effect of insulin (0.1-100 nM) on isometric force of contraction in isolated ground squirrel papillary muscle was investigated. In summer, autumn and winter active animals, insulin had a negative inotropic effect on papillary muscles, decreasing the amplitude of contraction by about 30% of the control value. In some cases, predominantly in the summer group of animals, insulin produced different effects on contractility: low doses (0.1-0.5 nM) caused a transient activation of isometric contraction by about 10-15% of control, whereas high doses produced a negative inotropic effect by about 30% of the control level. During deep hibernation (at 5-6 degrees C of heart temperature) and during arousal from hibernation (from 3 to 20 degrees C), insulin had no significant effect on contractility. Opposite inotropic effects of insulin at concentrations of 0.1-50 nM were found during arousal: from 26 to 31 degrees C of heart temperature--a positive inotropic effect by about 20-25% of control, and from 32 to 36 degrees C--a negative one by about 30-40% of the control value.

Myoglobin content in skeletal muscles of hibernating ground squirrels rises in autumn and winter.

The content of myoglobin (Mb) in skeletal muscles of Arctic Yakutian ground squirrel (Citellus undulatus Pallas) was measured in the active euthermic summer and prehibernating autumn animals as well as in hibernating and awake animals in winter. The myoglobin content in winter, irrespective of the state of the animal, was found to be about three times higher than in summer. The content of myoglobin in autumn was also two-fold increased compared to summer, suggesting that high myoglobin level is necessary for hibernation. Analysis of biochemical data available suggests that the increase in myoglobin content in winter is probably related to a high oxygen demand of muscles at the first stage of arousal (non-shivering thermogenesis) when rectal temperature rises from 0 to 10-12 degrees C. At this stage, the oxygen-dependent processes in muscles proceed under the conditions when peripheral blood flow is blocked and anaerobic glycolysis is switched off.

[The myoglobin level in skeletal muscles of the hibernating Iakutiia ground squirrel Citellus undulatus]. / Izucheniie soderzhaniia mioglobina v skeletnoi muskulature zimnespiashchego iakutskogo suslika Citellus undulatus.

Many characteristics of the ground squirrel metmyoglobin (Mb) were found to be similar to those of the pig and different from the whale ones. The Mb content in winter time was 2.5-3.0-fold higher in hibernating and arousing ground squirrels than in alert ones. This seems to be connected with the high demand of oxygen in the muscles at the first stage of arousal.

[Production of tumor necrosis factor (TNF) by macrophages and T-lymphocytes of rodents as affected by acute gamma-irradiation]. / Produktsiia faktora nekroza opukholei (FNO) makrofagami i T-limfotsitami gryzunov v usloviiakh ostrogo gamma-oblucheniia.

TNF production in peritoneal macrophages and in splenic T cell from mice and ground-squirrels were performed after acute in vivo and in vitro doses of ionizing radiation ranging from 0.1-6 Gy. It was observed that doses in the range 0.5-6 Gy induced the increase of TNF production along with the decrease of mitogen-induced proliferation in T lymphocytes.