[Chronic sleep restriction in rats leads to a weakening of compensatory reactions in response to acute sleep deprivation]. / Khronicheskoe ogranichenie sna u krys privodit k oslableniyu kompensatornykh reaktsii v otvet na ostruyu deprivatsiyu sna.

OBJECTIVE: To identify features in the compensatory mechanisms of sleep regulation in response to acute sleep deprivation after chronic sleep restriction in rats. MATERIAL AND METHODS: Male Wistar rats 7-8 months old underwent 5-day sleep restriction: 3 h of sleep deprivation and 1 h of sleep opportunity repeating throughout each day. Six-hour acute total sleep deprivation was performed at the beginning of daylight hours on the 3rd day after sleep restriction. Polysomnogramms were recorded throughout the day before chronic sleep restriction, on the 2nd recovery day after chronic sleep restriction and after acute sleep deprivation. The control group was not subjected to chronic sleep restriction. RESULTS: The animals after chronic sleep restriction had the compensatory increase in total sleep time in response to acute sleep deprivation weaker than in control animals. Animals after sleep restriction had the compensatory increase in the time of slow-wave sleep (SWS) only in the first 6 hours after acute sleep deprivation, whereas in control animals the period of compensation of SWS lasted 12 hours. A compensatory increase in slow-wave activity (SWA) was observed in both groups of animals, but in animals experiencing chronic sleep restriction the amplitude of SWA after acute sleep deprivation was less than in control animals. A compensatory increase in REM sleep in sleep restricted animals occurred immediately after acute sleep deprivation and coincides with a compensatory increase in SWS and SWA, whereas in control conditions these processes are spaced in time. CONCLUSION: Compensatory reactions in response to acute sleep deprivation (sleep homeostasis) are weakened in animals subjected to chronic sleep restriction, as the reaction time and amplitude are reduced.

[Modeling of chronic sleep restriction for translational studies]. / Sozdanie modeli khronicheskogo nedosypaniya dlya translyatsionnykh issledovanii.

OBJECTIVE: To develop of a chronic sleep restriction model in rats by repeated sleep deprivation using an orbital shaker and to determine whether this model leads to disturbances in sleep homeostatic mechanisms. MATERIAL AND METHODS: Male Wistar rats (7-8 months old) underwent sleep restriction for five consecutive days: 3 h of sleep deprivation and 1 h of sleep opportunity repeating throughout each day. Polysomnograms were recorded telemetrically throughout the day before sleep restriction (baseline), on the 1st, 3rd, 5th day of sleep restriction and 2 days after the end of sleep restriction (recovery period). RESULTS: During the period of sleep restriction, the total amount of slow-wave sleep (SWS) and rapid eye movement (REM) sleep decreased by 61% and 55%, respectively, compared to baseline. On the first day of recovery, amount of SWS increased mainly in the dark (active) phase of the day, while REM sleep increased in both light and dark phases; there was no marked rebound of daily SWS amount, while REM sleep increased by 30% from baseline. On the first day of recovery, an elevation of EEG beta and sigma power in sleep states was observed mainly in the light phase of the day. The loss of deep SWS throughout the sleep restriction period increased from 50% on 1st day to 75% on 5th day. The level of deep SWS remained below the baseline by 15-20% on the two subsequent days of recovery. The findings suggest that homeostatic mechanisms of SWS are persistently impaired after 5-day chronic sleep restriction. Besides, a decline of wakefulness accompanied by an increase of SWS in the active phase of the recovery period indicates a disruption in circadian rhythm. CONCLUSION: The proposed model leads to the disruption of sleep homeostatic mechanisms, which, in turn, impede compensation of SWS loss caused by chronic insufficient sleep.

[Age-related differences in sleep disturbances in rat models of preclinical Parkinson's disease]. / Vozrastnye osobennosti narushenii sna v modelyakh doklinicheskoi stadii bolezni Parkinsona u krys.

OBJECTIVE: To describe the changes in temporal characteristics of sleep-wake cycle, which can serve as non-motor manifestations of an early stage of Parkinson's disease (PD), using the model of preclinical PD in rats of two age groups. MATERIAL AND METHODS: A prolonged (up to 21 days) model of preclinical PD in middle-aged (7-8 month) and aged (19-20 month) rats was created. The model was based on cumulative inhibition of proteasomal system of the brain caused by intranasal administration of lactacystin, a specific proteasome inhibitor. Polysomnographic data were recorded daily using telemetric Dataquest A.R.T. System (DSI, USA) in unrestrained animals. RESULTS AND CONCLUSION: Aging was accompanied with increased sleepiness during the active (dark) phase of the day (as was implied by a two-fold increase in the total time of drowsiness) and with 1.5-fold growth of light sleep during the inactive phase of the day. A common feature of sleep disturbances in the model of preclinical PD in both middle-aged and aged rats was hypersomnia during the active phase of the day. It was suggested to be similar to the excessive daytime sleepiness in humans. Hypersomnolence was more pronounced in aged rats because it added to sleepiness developing with aging. In both age groups, the model of preclinical PD was also associated with a decrease in EEG delta power during slow-wave sleep. It is considered dangerous because it might represent the decrease in protein synthesis rate and the weakening of restorative processes in neurons, occurring with the prolonged inhibition of proteasomal system of the brain. Sleep disturbances, identified the model of preclinical PD in rats of different age, may be recommended for clinical validation as low-cost early signs indicating the initial stage of PD.

[U-133, a heat shock proteins inducer, precludes sleep disturbances in a model of the preclinical stage of Parkinson's disease in aged rats.]

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease, closely associated with aging. It is considered incurable due to both late diagnosis and symptomatic treatment, which is able to alter neither molecular mechanisms of sleep disruption nor the neurodegenerative processes, developing with aging and PD progression. In the present study, we assess the therapeutic potential of a novel chaperone inducer U-133 (acetyl 2,3,7-tris-O-glucoside echinochrome) in the preclinical stage of PD modelled in aged rats by the inhibition of the proteasomal system in the brain. U-133 is a derivative of the sea urchin pigment echinochrome (2,3,5,7,8-pentahydroxy-1,4-naphthoquinone) produced by glycosylation, which possesses neuroprotective, antioxidant, anticancer properties. The administration of U-133, inducing the synthesis of Hsp70i and Hdj1 heat shock proteins in the brain, precludes the increase of light sleep (drowsiness) stage and the decrease of deep slow-wave sleep total time, both occurring with the progression of the preclinical stage of PD modelled in aged Wistar rats. Deep slow-wave sleep is thought to promote glymphatic clearance and to accelerate protein synthesis. Thus, U-133-induced increase in deep slow-wave sleep percentage, as compared to the preclinical model, is considered having a neuroprotective effect that contributes to the intensification of the restorative function of neurons and counteracts the progressing neurodegeneration.

[Changes in characteristics of sleep-wake cycle and motor activity at the preclinical stage of Parkinson's disease in old rats]. / Izmeneniia kharakteristik sna i summarnoi dvigatel'noi aktivnosti v modeli doklinicheskoi stadii bolezni Parkinsona u starykh krys.

AIM: To assess the changes in temporal characteristics and total motor activity (MA) during the sleep-wake cycle in old rats in the model of the preclinical stage of Parkinson's disease (PD). MATERIAL AND METHODS: Progressing inhibition of proteasome system and prolonged (up to the 21st day) development of the preclinical stage of PD in 19-20-month Wistar rats was caused by the specific proteasomal inhibitor lactacystin administered twice with a week interval. Telemetric monitoring of sleep-wake cycle was performed along with the video recording of MA. Dopamine level in the dorsal striatum was measured by high-performance liquid chromatography. RESULTS: During the 13-21st days, the preclinical stage of PD in old rats was characterized by the following features: 1) increased drowsiness in the active (dark) phase of day that can be compared with the excessive daytime sleepiness in patients with PD; 2) growth of delta-activity indicating presumably a compensatory increase in the deep slow-wave sleep (SWS) stage; 3) decreased MA during SWS and drowsiness, which was coupled with the lowered dopamine level in the dorsal striatum typical for the preclinical stage of PD. CONCLUSION: Both increased drowsiness and reduced MA during sleep, reflecting dopamine deficit in the nigrostriatal system, may be recommended for using in clinical research as inexpensive early markers of the preclinical stage of PD.

[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.