Preventive Administration of the Heat Shock Protein Hsp70 Relieves Endotoxemia-Induced Febrile Reaction in Pigeons ( Columba livia ) and Rats.

The stress-inducible 70 kDa heat shock protein (Hsp70) can exert a protective effect on endotoxemia and sepsis due to its ability to interact with immune cells and modulate the immune response. However, it remains unknown whether Hsp70 is able to relieve endotoxemia-induced fever. We carried out a comparative study of the effects of preventive administration of the human recombinant Hsp70 (HSPA1A) on lipopolysaccharide (LPS)-induced endotoxemia in pigeons and rats with preimplanted electrodes and thermistors for recording the thermoregulation parameters (brain temperature, peripheral vasomotor reaction, muscular contractile activity). Additionally, we analyzed the dynamics of the white blood cell (WBC) count in rats under the same conditions. It was found that preventive administration of Hsp70 relieves the LPS-induced febrile reaction in pigeons and rats and accelerates the restoration of the WBC count in rats. The data obtained suggest that these warm-blooded animals share a common physiological mechanism that underlies the protective effect of Hsp70.

[A study of participation of Hdj1 co-chaperone in the modulation of sleep and behavior using micro RNA technology in vivo].

Data obtained for the last 12 years and modern hypotheses on key function of sleep and the role of Heat Shock Protein 70 kDa (HSP70) molecular chaperones family in sleep modulation are insufficient to determine assotiation of sleep quantity to the level of chaperones in the basic "center" of sleep in the ventrolateral preoptic area (VLPA) of the hypothalamus. In the present study, to reduce the content of Hdj1 major co-chaperone of Hsp70 in the VLPA we employed a novel approach based on lentiviral construction containing specific Hdj1-shRNA. The immunoblotting data showed that in 6 weeks after infection the level of Hdj1 in VLPA was reduced by 80% that was accompanied by a considerable increase in the quantity of slow-wave sleep and a marked decrease in the level of anxiety; earlier we found that elevation of Hsp70 level in the rat brain resulted in similar changes. It is suggested that the increase in quantity of slow wave sleep and the decrease in the level of anxiety can be related to a sustained disorder in the integration between molecular systems based on chaperones Hdj1 and Hsp70 and to a compensatory increase in the Hsp70 chaperone activity/level in VLPA.

[Study of the protective effects of exogenous heat shock protein 70 kDa in the model of sleep deprivation in pigeons Columba livia].

Electroencephalographic methods were used to study effects of the preparation of the exogenous heat shock protein with molecular mass 70 kDa (Hsp70i/Hsc70) on the time characteristics of sleep and waking, brain temperature, peripheral vasomotor reactions and thoracic muscle contractile activity after the 5-hour sleep deprivation in pigeons (Columba livia). The microinjections of Hsp70i/Hsc70 were performed into the third brain ventricle after the end of sleep deprivation. It was shown that Hsp70i/Hsc70 eliminated the disturbances of sleep-wake cycle and evoked a decrease in the thoracic muscle contractile and brain temperature during the first hour of postdeprivation period. During the following hours Hsp70i/Hsc70 evoked an increase in the total time of deep sleep and a decrease in the total time of rapid-eye-movement sleep. We suppose that the protective effects of Hsp70i/Hsc70 could be associated with its capacity to weaken the activity of the hypothalamo-hypophyseal-adrenal axis and to enhance the stress-limiting function of non-rapid-eye-movement sleep.

Effects of sleep deprivation on measures of the febrile reaction and the recovery of somatovisceral functions and sleep in endotoxemia.

Electroencephalographic methods were used to study the effects of total sleep deprivation on thermoregulatory measures of the fever response in pigeons (Columba livia): brain temperature, peripheral vasomotor reactions, thoracic muscle contractile activity, and the recovery of somatic functions and the time characteristics of waking and sleep in lipopolysaccharide (LPS)-induced endotoxemia. Sleep deprivation during the period in which the quantity of slow-wave sleep increased on administration of LPS induced decreases in the latent period of fever onset and in the duration of fever, along with more significant increases in brain temperature and the level of muscle contractile activity as compared with the effects of LPS alone. The period after sleep deprivation was characterized by more prolonged recovery of muscle contractile activity and the time characteristics of sleep and waking states, along with more prolonged compensatory "rebound" of slow-wave sleep as compared with the effects of sleep deprivation alone. Thus, sleep deprivation in endotoxemia led to decreases in the latent period of fever onset, exacerbation of fever, and increases in the latent period of recovery of physiological functions.

[Effect of sleep deprivation on characteristics of febrile reaction and process of restoration of the somato-visceral functions during endotoxaemia].

Using electrophysiological methods, the effects of total sleep deprivation on thermoregulatory characteristics of the febrile reaction (brain temperature, peripheral vasomotor reaction, contractile activity of the pectoral muscle), the process of rehabilitation of somatic functions, and temporal characteristics of wakefulness and sleep during the endotoxaemia caused by the bacterial endotoxin lipopolysaccharide (LPS) in pigeons (Columba livia) were studied. It was shown that sleep deprivation during the period of the augmentation of non-rapid-eye-movement sleep in result of the LPS injection evoked a decrease in latency of the fever development and fever duration and caused a more pronounced rise of the brain temperature and the level of contractile muscular activity in comparison with the effects of LPS. The period after sleep deprivation was characterized by a more prolonged recovery of the level of contractile muscular activity and temporal characteristics of sleep and wakefulness and more prolonged compensatory rebound of non-rapid-eye-movement sleep in comparison with the effect of sleep deprivation alone. Thus the realization of sleep deprivation during endotoxaemia evoked a decrease in latency of the fever development and the reinforcement of fever; and an increase in latency of the restoration of physiological functions.