Phosphorylation and Dephosphorylation of Tau Protein During Synthetic Torpor.

Tau protein is of primary importance for many physiological processes in neurons, where it affects the dynamics of the microtubule system. When hyperphosphorylated (PP-Tau), Tau monomers detach from microtubules and tend to aggregate firstly in oligomers, and then in neurofibrillary tangles, as it occurs in a group of neurodegenerative disorders named thauopathies. A hypothermia-related accumulation of PP-Tau, which is quickly reversed after the return to normothermia, has been shown to occur in the brain of hibernators during torpor.

c-Fos expression in the limbic thalamus following thermoregulatory and wake-sleep changes in the rat.

A cellular degeneration of two thalamic nuclei belonging to the "limbic thalamus", i.e., the anteroventral (AV) and mediodorsal (MD) nuclei, has been shown in patients suffering from Fatal Familial Insomnia (FFI), a lethal prion disease characterized by autonomic activation and severe insomnia.

REM Sleep and Endothermy: Potential Sites and Mechanism of a Reciprocal Interference.

Numerous data show a reciprocal interaction between REM sleep and thermoregulation. During REM sleep, the function of thermoregulation appears to be impaired; from the other hand, the tonic activation of thermogenesis, such as during cold exposure, suppresses REM sleep occurrence. Recently, both the central neural network controlling REM sleep and the central neural network controlling thermoregulation have been progressively unraveled.

Wake-sleep and cardiovascular regulatory changes in rats made obese by a high-fat diet.

Obesity is known to be associated with alterations in wake-sleep (WS) architecture and cardiovascular parameters. This study was aimed at assessing the possible influence of diet-induced obesity (DIO) on sleep homeostasis and on the WS state-dependent levels of arterial pressure (AP) and heart rate in the rat. Two groups of age-matched Sprague-Dawley rats were fed either a high-fat hypercaloric diet, leading to DIO, or a normocaloric standard diet (lean controls) for 8 weeks.

Wake-sleep, thermoregulatory, and autonomic effects of cholinergic activation of the lateral hypothalamus in the rat: a pilot study.

A major role in the wake-promoting effects of the activation of the lateral hypothalamus (LH) has been ascribed to a population of orexin (ORX)-containing neurons that send projections to central areas which regulate Wake-Sleep and autonomic function. Since, in the rat, a substantial amount of ORX neurons receive cholinergic projections from cells involved in Wake-Sleep regulation, the aim of this study was to assess the role played by LH cholinoceptive cells in Wake-Sleep and autonomic regulations. To this end, the effects of a microinjection of the cholinergic agonist Carbachol (CBL) into the LH were compared to those obtained through the activation of a wider cell population by the microinjection of the GABAA antagonist GABAzine (GBZ).

Evidence of a diurnal thermogenic handicap in obesity.

A thermogenic handicap has been proposed as potential contributor to weight gain in obese subjects but results from clinical studies are inconclusive. We tested whether diurnal and nocturnal body core temperature (BcT) measured for 20-h differed in nine obese subjects compared with 12 lean healthy controls when studied at rest under strictly controlled conditions. BcT was significantly reduced (∼0.

Enhanced slow-wave EEG activity and thermoregulatory impairment following the inhibition of the lateral hypothalamus in the rat.

Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be the consequence of the inhibition of specific neuronal populations within the LH, i.

The direct cooling of the preoptic-hypothalamic area elicits the release of thyroid stimulating hormone during wakefulness but not during REM sleep.

Thermoregulatory responses to temperature changes are not operant during REM sleep (REMS), but fully operant in non-REM sleep and wakefulness. The specificity of the relationship between REMS and the impairment of thermoregulation was tested by eliciting the reflex release of Thyrotropin Releasing Hormone (TRH), which is integrated at hypothalamic level. By inducing the sequential secretion of Thyroid Stimulating Hormone (TSH) and Thyroid Hormone, TRH intervenes in the regulation of obligatory and non-shivering thermogenesis.

Waking and sleeping in the rat made obese through a high-fat hypercaloric diet.

Sleep restriction leads to metabolism dysregulation and to weight gain, which is apparently the consequence of an excessive caloric intake. On the other hand, obesity is associated with excessive daytime sleepiness in humans and promotes sleep in different rodent models of obesity. Since no consistent data on the wake-sleep (WS) pattern in diet-induced obesity rats are available, in the present study the effects on the WS cycle of the prolonged delivery of a high-fat hypercaloric (HC) diet leading to obesity were studied in Sprague-Dawley rats.

The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat.

The possibility of inducing a suspended animation state similar to natural torpor would be greatly beneficial in medical science, since it would avoid the adverse consequence of the powerful autonomic activation evoked by external cooling. Previous attempts to systemically inhibit metabolism were successful in mice, but practically ineffective in nonhibernators. Here we show that the selective pharmacological inhibition of key neurons in the central pathways for thermoregulatory cold defense is sufficient to induce a suspended animation state, resembling natural torpor, in a nonhibernator.

Waking and sleeping following water deprivation in the rat.

Wake-sleep (W-S) states are affected by thermoregulation. In particular, REM sleep (REMS) is reduced in homeotherms under a thermal load, due to an impairment of hypothalamic regulation of body temperature. The aim of this work was to assess whether osmoregulation, which is regulated at a hypothalamic level, but, unlike thermoregulation, is maintained across the different W-S states, could influence W-S occurrence.

Hypothalamic osmoregulation is maintained across the wake-sleep cycle in the rat.

In different species, rapid eye movement sleep (REMS) is characterized by a thermoregulatory impairment. It has been postulated that this impairment depends on a general insufficiency in the hypothalamic integration of autonomic function. This study aims to test this hypothesis by assessing the hypothalamic regulation of body fluid osmolality during the different wake-sleep states in the rat.

c-Fos expression in preoptic nuclei as a marker of sleep rebound in the rat.

Thermoregulation is known to interfere with sleep, possibly due to a functional interaction at the level of the preoptic area (POA). Exposure to low ambient temperature (T(a)) induces sleep deprivation, which is followed by sleep rebound after a return to laboratory T(a). As two POA subregions, the ventrolateral preoptic nucleus (VLPO) and the median preoptic nucleus (MnPO), have been proposed to have a role in sleep-related processes, the expression of c-Fos and the phosphorylated form of the cAMP/Ca(2+)-responsive element-binding protein (P-CREB) was investigated in these nuclei during prolonged exposure to a T(a) of -10 degrees C and in the early phase of the recovery period.

Cold exposure and sleep in the rat: REM sleep homeostasis and body size.

Study Objectives: Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24 degrees C.

Design: EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10 degrees C to -10 degrees C and for 4 days during recovery.

Cold exposure impairs dark-pulse capacity to induce REM sleep in the albino rat.

In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during exposure to low ambient temperature (Ta). To this aim, the efficiency of a non-rhythmical repetitive DP (3 min each) delivery during the first 6-h light period of a 12 h:12 h light-dark cycle in inducing REMS was studied in the rat, through the analysis of electroencephalogram, electrocardiogram, hypothalamic temperature and motor activity at different Tas.

Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat.

The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake-sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP(3) in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature (T(a)). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory T(a); (iv) a significant increase of IP(3) concentration in CC following exposure to low T(a). The earliest and most sensitive effects of lithium appear to be those concerning sleep.

Cold exposure and sleep in the rat: effects on sleep architecture and the electroencephalogram.

Study Objectives: Acute exposure to low ambient temperature modifies the wake-sleep cycle due to stage-dependent changes in the capacity to regulate body temperature. This study was carried out to make a systematic analysis of sleep parameters during the exposure to different low ambient temperatures and during the following recoveries at ambient temperature 24 degrees C.

Design: Electroencephalographic activity, hypothalamic temperature, and motor activity were studied during a 24-hour exposure to ambient temperatures ranging from 10 degrees C to -10 degrees C and for 4 days during the recovery.

Changes in EEG activity and hypothalamic temperature as indices for non-REM sleep to REM sleep transitions.

A shift of physiological regulations from a homeostatic to a non-homeostatic modality characterizes the passage from non-NREM sleep (NREMS) to REM sleep (REMS). In the rat, an EEG index which allows the automatic scoring of transitions from NREMS to REMS has been proposed: the NREMS to REMS transition indicator value, NIV [J.H.

Specific changes in cerebral second messenger accumulation underline REM sleep inhibition induced by the exposure to low ambient temperature.

In the rat the exposure to an ambient temperature (Ta) of -10 degrees C induces an almost total REM sleep deprivation that results in a proportional rebound in the following recovery at normal laboratory Ta when the exposure lasts for 24 h, but in a rebound much lower than expected when the exposure lasts 48 h. The possibility that this may be related to plastic changes in the nervous structures involved in the control of thermoregulation and REM sleep has been investigated by measuring changes in the concentration of adenosine 3':5'-cyclic monophosphate (cAMP) and D-myo-inositol 1,4,5-trisphosphate (IP(3)) in the preoptic-anterior hypothalamic area (PO-AH), the ventromedial hypothalamic nucleus (VMH) and, as a control, the cerebral cortex (CC). Second messenger concentration was determined in animals either stimulated by being exposed to hypoxia, a depolarizing condition that induces maximal second messenger accumulation or unstimulated, at the end of a 24-h and a 48-h exposure to -10 degrees C and also between 4 h 15 min and 4 h 30 min into recovery (early recovery).

Single and Sequential REM sleep episodes in humans: a phylogenetic left-over?

The occurrence of REM sleep in the rat appears to be under the control of either sleep related processes and homeostatic regulation of physiological variables. With respect to this, it has been observed that in this species REM sleep may occur in the form of two types of episodes, Single and Sequential episodes, which are supposed to play a different functional role. Since it is possible to distinguish Single and Sequential REM sleep episodes also in human beings, the aim of this pilot study was to asses whether a sleep deprivation may differently affect these two types of REM episodes.