[Changes in the characteristics of paradoxical sleep are an early feature of Parkison's disease].

Data on the sleep disorders in patients with Parkinson's disease are given. The basic point focuses on analysis of paradoxical sleep without muscle atonia. The author reports developed models of preclinical and clinical stages of Parkinson's disease in Wistar rats on the basis ofa moderate and deep attenuation in activity of ubiquitin-proteasome system, a key mechanism of aging and development of conformation disease. The hypothesis about changes in the characteristics of paradoxical sleep as a marker of parkinsonism stages is validated. It reflects the state of compensator and neuroprotective reserves of nigrostriatal dophaminergic system.

[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.

[Content of chaperon Hsp70 in dopaminergic neurons of the black substance increases in proteasome dysfunstion].

In Wistar rats, specific inhibitor UPS lactacystin induced degeneration of 24% of the dopaminergic neurons in the black substance. The work shows that a moderate weakening of the UPS function is characterized by an enhanced activity of the shaperon system. This process seems to restore and maintain population of the dopaminergic neurons.

[Thermophysiology of the paradoxical sleep].

Data on interactions between the paradoxical sleep (PS) and thermoregulation under thermo-comfortable and extreme conditions (in high and low temperatures, forced and spontaneous fasting, acclimation to cold and acclimation to natural winter conditions) are reviewed. The hypothesis of the PS role in synchronising and endogenous "kindling" of the visceral function ultradian rhythms is substantiated. Some new data are presented on entering torpor as a phenomenon of the "dramatic" neuronal plasticity.

[Effects of thermal preconditioning on convulsive activity in rats with inheritable form of audiogenic epilepsy].

Effects of thermal preconditioning universal recognized method of increase in concentration of inducible Heat shock protein 70 kDa (Hsp70i) on characteristics of convulsive activity in Krushinskii-Molodkina (KM) rats with inheritable audiogenic epilepsy were studied. For the first time, it was found that short-term thermal preconditioning (41 degrees C during 5 minutes) increased duration of the latency of audiogenic seizure onset. Thermal preconditioning resulted in an increase in concentration of Hsp70i in amygdale, hypothalamus, midbrain; the uttermost increase was observed in hippocampus and inferior colliculus: the brain areas responsible for initiation of audiogenic seizures. A coincidence was found in the term of increase in concentration of Hsp70i and the latency of seizure onset (on day 4 after thermal preconditioning). Results of this research confirm the proposition that inducible Hsp70i is capable of taking part in the processes of seizure development in rats with inheritable form of audiogenic epilepsy.

[Chaperones in regulation and restoration of physiological functions].

Protective effects of the HSP70 expression in heat stress, sleep deprivation, epilepsy, enhanced anxiety, psycho-emotional stress, physical loads, are described, and data on the HSP70 effects upon characteristics of sleep and somatic-visceral functions in homeothermic animals are cited. Prospects of using the HSP70 "inductors" are discussed as well as the HSP70 preparations use in therapy of large range of pathological conditions.

[EFfect of quercetin on the severity of chemically induced seizures and the content of heat shock protein 70 in the rat brain structures].

Effects of the inhibitor of the expression of Heat shock proteins 70 kDa (Hsp70), quercetin on seizures and movement disorders induced by N-methyl D-aspartate (NMDA) or pentylenetetrazole in adult rats Wistar were investigated using behavioral methods. It was found that intraperitoneal injection of quercetin 4 hours before intraventricular microinjection of NMDA resulted in increased duration of tonic component of seizures, seizure and ataxia symptoms severity. Blockade of the expression of Hsp70 by quercetin increased the duration of clonic and tonic seizures and did not affect severity of seizures and ataxia symptoms, induced by intraperitoneal injection of pentylenetetrazole. Immunoblotting showed that injection of quercetin resulted in reduced content of the inducible form of Hsp70 in the hippocampus, thalamus and corpus callosum. The obtained results indicate proconvulsant effect of quercetin associated with the inhibition of Hsp70 expression. These data suggest involvement of Hp70 in regulation of central mechanisms of behavioral seizures and motor disorders induced by NMDA and pentylenetetrazole in rats.

[Sleep changes during degeneration of neurons in the substantia nigra induced by inhibitor of proteasomes lactacystin in rats].

A decrease in activity of ubiquitin proteasome system results in accumulation of toxic forms of protein and cell degeneration, including dopamine (DA)-ergic neurons in the substantia nigra; these neurons are remarkable for their low proteolytic activity of proteosomes that makes them more vulnerable, especially when subjected to the neurotoxin action or Parkinson's disease (PD). The goal of the present study is to develop a model on the basis of inhibition of proteasome activity of nigral cell degeneration which is not accompanied by disturbances in motor behavior but leads to changes in sleep-wake cycle characteristic of the non-motor behaviour. We determined the optimal dose of natural inhibitor of proteasome lactacystin (0.4 mkg) and developed a preclinical model of PD in Wistar rats. We established that on the 14th day following lactacystin double (with one-week interval) bilateral injection into the substantia nigra the developing effects involved 28 % degeneration of DA-ergic neurons in the compact part of the substantia nigra, absence of disorders in motor behaviour, and increase in the total time of rapid eye movement sleep by 37 % at the second half of inactive day phase. These data and an increase in the level of key enzyme of DA synthesis tyrosine hydroxylase (TH) in survived neurons in the substantia nigra as well as the presence of the inverse correlation dependency (r = -0.8, p < 0.01) between the number of survived neurons and the level of TH inside them suggest a hypothesis that the increase in the duration of rapid eye movement sleep could be a non-motor marker of the preclinical stage of PD reflecting a reservation of compensatory potentials in the nigrostriatal system.

[Microinjections of heat shock protein 70 kDa into the nucleus reticularis pontis oralis induce inhibition of rapid eye movement sleep in pigeons].

Recently it was indicated that microinjections of heat shock proteins 70 kDa (Hsp70) into the third ventricle of brain in pigeons results in an increase in the duration of slow wave sleep and a decrease in somato-visceral indices. It is suggested that Hsp70 effect may be related to GABA(A) receptors activation in the preoptic area of the hypothalamus. However, what transmitter mechanisms of activation are related to the removal effect (in 2-3 hrs) of rapid eye movement sleep inhibition still remains poorly understood. To solve this problem in the present study, microinjections of Hsp70 into the Nucleus reticularis pontis oralis (NRPO) were done. It is well known that cholinergic neurons of the NRPO are crucial for rapid eye movement sleep generation. The data show that Hsp70 produces more early (for first two hrs) a decrease in number of episodes and total time of rapid eye movement sleep, a diminution of electroencephalogram (EEG) power spectra in the 9-14 Hz band, a decrease in contractile muscle activity and brain temperature. It is suggested that Hsp70 effects are realized due to activation of GABA(A) receptors in the NRPO and induced inhibition of cholinergic mechanisms of rapid eye movement sleep triggering. The microinjections of Hsp70 into the NRPO increase the slow wave sleep total time with long latency (for 8-12 hrs). This effect may be related to influence of Hsp70 on neurons population, which are responsible for slow wave sleep maintenance outside the NRPO.

[Protein 70 kDa in control of sleep and thermoregulation].

Studies of expression of molecular chaperones of the family of Heat Shock Proteins 70 kDa (HSP70) in the mouse and rat brain during sleep deprivation do not answer the question whether the HSP70 produce somnogenic effect. In the present work there are studied effects of exogenous Hsp70 that is known to be able to penetrate into living cells in vitro and to acquire properties of endogenous chaperone. Hsp70 was microinjected into the third brain ventricle of rats and pigeons at the beginning of the inactive period of the day when under natural conditions the sleep duration increases and the somato-visceral parameters decrease. Hsp70 was found to enhance this natural process and to produce an additional increase in the total time of slow-wave sleep, a more pronounced inhibition of the muscle contractive activity, and a deeper decrease in the brain temperature. A similarity in effects of Hsp70 in rats and pigeons was revealed. In both species the somnogenic effect of Hsp70 in is realized by activation of mechanisms of maintenance of in longer episodes of in slow-wave sleep. The hypothermic Hsp70 effect seems to be associated with a decrease in the muscle contractive activity level, rather than with an enhancement in peripheral vasodilation and with an increase of heat loss. A hypothesis is put forward that the neuroleptic effect of Hsp70 that includes the somnogenic, myorelaxing, and hypothermic effects is mediated by activation of GABAA receptors of the main inhibitory brain system.

[Participation of muscarinic and nicotinic cholinoreceptors of hypothalamus preoptic area in control of wakefulness and sleep states and of thermoregulation in pigeons Columbia livia].

By using electrophysiological methods, it has been established that muscarinic (M-) cholinergic mechanisms of the ventrolateral preoptic area (VLPA) of pigeon hypothalamus participate in maintenance of wakefulness, whereas nicotinic (N-) mechanisms--in maintenance of the slow-wave sleep. Activation of the VLPA M-cholinergic receptors has been found to be accompanied by an elevation of the brain temperature, by development of peripheral vasoconstriction, and by an increase in the muscle contractive activity. Activation of N-cholinoreceptors leads to a decrease in the brain temperature and development of peripheral vasoconstriction. It is suggested that the VLPA M- and N-cholinergic receptors are involved in different mechanisms of regulation of wakefulness and sleep states and brain temperature in pigeons.

[Role of cholinergic mechanisms of the ventrolateral preoptico-anterior hypothalamic area in regulation of sleep and wakefulness states in pigeons].

Maintenance of wakefulness is established to accomplish muscarinic (M-) cholinergic receptor activation in the ventrolateral preoptic area of the hypothalamus. The "muscarinic" wakefulness is characterized by enhancement of electroencephalogram (EEG) power spectra in the 0.75-12 Hz band and by increase in brain temperature. Activation of nicotinic (N-) cholinergic receptors of the area produces an increase in the duration of slow wave sleep, EEG power spectra reduction in the 0.75-7 Hz band, a decrease in brain temperature. And its hyperactivation leads to wakefulness, during its episodes the brain temperature decreases. During M- and N-cholinergic receptor blockade, the sleep-wakefulness and thermoregulation changes opposite to their activation were found. It is suggested that M- and N-cholinergic receptors of the ventrolateral preoptic area in pigeons participate in the sleep-wakefulness regulation and this effect is related to influence of this area on GABA-ergic system.

[Circadian and seasonal changes in the temperature-regulating behavior of the American ground squirrel Citellus parryi]. / Sutochnye i sezonnye izmeneniia termoreguliatsionnogo povedeniia u amerikanskogo suslika Citellus parryi.

Under uninterrupted (during 10 days) temperature registration from 4 nest boxes ("thermogradient" plant) clear-cut changes were determined: in preferable temperature (PT, degrees C, in 24 hrs at an average)--21.0 +/- 0.5 (spring), 22.7 +/- 0.3 (summer), 18.8 +/- 0.7 (autumn), 11.5 +/- 0.5 (period before hibernation-PBH), 7.5 +/- 7.9 (hibernation season); in locomotor activity duration (LA, per cent from 24 hrs) which has decreased from 29.6% in spring to 20.3% at PBH (p < 0.001), and approximately to 2-3% during hibernation season; and in body mass which has varied from 350 g in spring to 750 at PBH. An increase in LA circadian rhythm amplitude was revealed in autumn, and the appearance and a rapid increase in PT circadian rhythm amplitude were observed at the beginning of PBH. A stage-to-stage "upswinging" of activity/rest circadian rhythms (stage I) and of thermoregulatory behavior (stage II) are supposed to occur at the end of euthermy season, which promotes synchronizing of the physiological processes and extending of the thermoneutra zone before the entrance into torpor and hibernation.