Plasma corticosterone elevation inhibits the activation of nuclear factor kappa B (NFKB) in the Syrian hamster pineal gland.

We evaluated how the mild stress-induced increase in endogenous corticosterone affected the pineal gland in Syrian hamsters (Mesocricetus auratus). The animals were maintained under constant light for 1 day, instead of a cycle of 14:10-h, to increase the circulating corticosterone levels during the daytime. The nuclear translocation of nuclear factor kappa B (NFKB), which is the pivotal transcription factor for stress and injury, presented a daily rhythm in normal animals. NFKB nuclear content increased linearly from the onset of light [Zeitgeber Time 0 (ZT0)] until ZT11 and decreased after ZT12 when the plasma corticosterone peak was detected in normal animals. However, the 24-h profiles of the two curves were different, and they did not clearly support an exclusive relationship between corticosterone levels and NFKB content. Therefore, we tested the effect of increased endogenous corticosterone through inducing mild stress by maintaining daytime illumination for one night. This stressful condition, which increased daytime corticosterone levels, resulted in a daytime decrease in NFKB nuclear content, and this was inhibited by mifepristone. Overall, this study shows that NFKB has a daily rhythm in Syrian hamster pineal glands and, by increasing endogenous corticosterone with a stressful condition, NFKB activity is regulated. Therefore, this study suggests that the pineal gland in the Syrian hamster is a sensor of stressful conditions.

Local corticosterone infusion enhances nocturnal pineal melatonin production in vivo.

Melatonin, an important marker of the endogenous rhythmicity in mammals, also plays a role in the body defence against pathogens and injuries. In vitro experiments have shown that either pro- or anti-inflammatory agents, acting directly in the organ, are able to change noradrenaline-induced pineal indoleamine production. Whereas corticosterone potentiates melatonin production, incubation of the gland with tumour necrosis factor-alpha decreases pineal hormonal production. In the present study, we show that nocturnal melatonin production measured by intra-pineal microdialysis is enhanced in pineals perfused with corticosterone at concentrations similar to those measured in inflamed animals. In vitro experiments suggest that this enhancement may be due to an increase in the activity of the two enzymes that convert serotonin to N-acetylserotonin (NAS) and NAS to melatonin. The present results support the hypothesis that the pineal gland is a sensor of inflammation mediators and that it plays a central role in the control of the inflammatory response.

Melatonin in the multi-oscillatory mammalian circadian world.

In mammals, the complex interaction of neural, hormonal, and behavioral outputs from the suprachiasmatic nucleus (SCN) drives circadian expression of events, either directly or through coordination of the timing of peripheral oscillators. Melatonin, one of the endocrine output signals of the clock, provides the organism with circadian information and can be considered as an endogenous synchronizer, able to stabilize and reinforce circadian rhythms and to maintain their mutual phase-relationship at the different levels of the circadian network. Moreover, exogenous melatonin, through an action on the circadian clock, affects all levels of the circadian network. The molecular mechanisms underlying this chronobiotic effect have also been investigated in rats. REV-ERB alpha seems to be the initial molecular target.

Seasonal variations in the nycthemeral rhythm of plasma melatonin in the camel (Camelus dromedarius).

Seasonal changes in the pattern of plasma melatonin were investigated in two groups of camels (Camelus dromedarius): 11 adult and six young camels. Animals were subjected to the outdoor conditions of a desert environment. Blood samples were taken at regular intervals of about 3 hr (added to particular samples at 1 hr before then 30 min and 1 hr after sunset, and 1 hr before and 1 hr after sunrise) for 24 hr at both solstices and equinoxes of the year. The plasma melatonin levels steeply increased soon after sunset and remained elevated throughout all the night. Then, melatonin concentrations progressively declined shortly before sunrise and returned to daytime basal levels 1 hr later. There was no seasonal variation in the amplitude or in the offset of the melatonin peak or in the daytime basal levels. The onset of the nocturnal peak was delayed by 2 hr in June at the summer solstice (P < 0.05), which can be related to the changes in night length between the two solstices. A significant effect of age was observed in all seasons. Melatonin levels were higher in the young camel group (fall equinox: P < 0.001; spring equinox: P < 0.01; winter solstice: P < 0.01; summer solstice: P < 0.05). The pattern of melatonin secretion in the camel showed a significant seasonal variation parallel to the photoperiodic changes of the year. The observed decline of melatonin levels during an extra-light pulse in the middle of the night indicates the light control of melatonin synthesis. It is not yet known if, in this low latitude desert region, the seasonal breeding period of the camel is cued by the photoperiod. The data obtained, however, clearly demonstrate that the camel has the capacity to follow and to integrate photoperiodic changes through melatonin changes.

The chronobiotic properties of melatonin.

In mammals, the exact role of melatonin (Mel) in the circadian timing system remains to be determined. However, exogenously administered Mel, as reported in the present mini-review, has been shown to affect the circadian clock. The sites and mechanisms of action involved in this "chronobiotic" effect of Mel have begun to be characterized. The suprachiasmatic nuclei (SCN) appear to be an important site for the entrainment effect of Mel and the presence of Mel receptors appears to be a prerequisite. However, the pharmacological dose of Mel needed to entrain circadian rhythms means that very probably other sites and mechanisms also play a role.

Potentiation effect of vasopressin on melatonin secretion as determined by trans-pineal microdialysis in the Rat.

The mammalian pineal gland is known to receive a noradrenergic innervation originating from the superior cervical ganglion which corresponds to the primary regulatory input for melatonin synthesis. However, many peptidergic fibers containing peptides such as vasopressin and oxytocin have also been found in the rat pineal gland. The present study was performed to investigate the possible role of vasopressin and oxytocin on melatonin secretion in vivo. Therefore, both neuropeptides were delivered for 2 h through a trans-pineal microdialysis probe directly into the gland at different times during the nocturnal phase of the light:dark cycle. At the same time pineal dialysates were collected continuously. Melatonin concentrations were measured by radioimmunoassay. Melatonin synthesis potentiation was achieved when vasopressin was infused locally in the pineal, during the onset of nocturnal melatonin secretion. In order to assess the possible role of a physiological increase of endogenous circulating vasopressin on pineal metabolism, melatonin synthesis was recorded in the same animals before and after a prolonged dehydration period. Night time melatonin concentration was increased after the water deprivation vs control conditions. Contrary to that, oxytocin seems not to affect pineal metabolism in the rat since no significant change was observed on melatonin secretion in response to a local oxytocin infusion. These results show that vasopressin can modulate melatonin synthesis in the rat pineal whereas no effect was obtained with oxytocin, at least under the present experimental conditions.

Interindividual differences in the pattern of melatonin secretion of the Wistar rat.

In vivo trans-pineal microdialysis was performed in male Wistar rats maintained under a 12 hr light:12 hr dark (LD 12:12) cycle. Collected dialysates were assayed by radioimmunoassay for melatonin concentrations. A non-linear regression was fitted through the obtained datapoints to determine the time points at which a 50% increase (IT50) and decrease (DT50) of the nocturnal melatonin peak were reached. In a first experiment, the nocturnal melatonin profiles of four animals were determined throughout 5 consecutive days. In a second experiment, we analysed the melatonin profiles during the night in rats originating from three different breeding colonies (Dépré Harlan, and Iffa-Credo). A low intraindividual variability was found on the phase markers IT50 and DT50, as on peak duration of melatonin rhythms estimated over 5 subsequent days in the same animal. In contrast, animals showed a large interindividual variability in their profile phase markers and the values were dependent on the origin of the breeding colony. Each rat colony was characterized by early or late IT50 and DT50 as long or short peak length. It is concluded from experiment 1 that the melatonin rhythm is a very stable circadian marker. Nevertheless, great caution must be taken in the choice of animal groups while studying circadian rhythms due to the large interindividual variability observed in experiment 2. Therefore, as the technique allows the use of the animal as its own control, the present study demonstrated that the use of the microdialysis technique is of interest in studies on the circadian system.

A short-term poikilothermic period occurs just after paradoxical sleep onset in humans: characterization changes in sweating effector activity.

We examined the changes in sudorific effector activity in five healthy young (21-23 y) subjects just before, during and just after successive paradoxical sleep (PS) phases. Local sweat rates were evaluated minute by minute over the chest (mcs). Previous observations, showing that mcs levels dropped before paradoxical sleep onset was electrophysiologically scored, were confirmed. At the end of this period of mcs depression, which in the present study coincided with paradoxical sleep onset, we show for the first time a short period (3-7 min) (period I) during which sweat production completely disappeared. A second period then followed (period II), at the very beginning of which mcs was re-elicited and thereafter increased in close correlation with paradoxical sleep duration. During period II, the remaining inhibiting influences (maximal during period I) and their releases could be specified by the successive valleys (indicating mcs inhibition) and peaks (indicating release of the mcs inhibition) drawn by the minute by minute mcs changes. These inhibitions became weaker as paradoxical sleep advanced. Given the strategic position of period I (at paradoxical sleep onset) and the total mcs abolition therein observed, it may be assumed that this poikilothermic state is the re-emergence of the 'ancestral' mode of body temperature regulation. From a thermophysiological point of view, period II may be considered as more 'modern' and directly related to the extension of paradoxical sleep in humans. This extension could be underlain by the unique development of our cognitive and/or learning functions.

Effects of local restriction of evaporation and moderate local ventilation on thermoregulatory responses in exercising humans.

Ten healthy young men participated in two series of three trials: series 1 (C1) with, or without, local restriction of evaporation (either on the trunk or on the legs) and series 2 (C2) with, or without, local moderate nitrogen ventilation (40 l.min-1) under an impermeable garment (trunk or leg ventilation). After 60-min rest in a thermoneutral environment, the subjects exercised in a warm environment [30 degrees C, 47% relative humidity (rh) during C1 and 29% rh during C2] on a cycle ergometer for 60 min at 70 W during C1 or at 60 W during C2. During C1, local covering with plastic foil did not increase internal temperature, but increased the mean skin temperature with a higher effect in the case of leg restriction. The trunk skin temperature was affected by the leg covering while the leg skin temperature was not changed by the trunk covering. Only the local sweat rate of the trunk was increased by the two restriction conditions. During C2, internal temperature was decreased by local ventilation while mean skin temperature was reduced only by trunk ventilation. The local ventilation affected only trunk skin temperature with a greater decrease during trunk ventilation. Trunk ventilation did not influence the skin temperature of the legs while ventilation of the legs decreased trunk skin temperature. In addition, leg ventilation decreased the sweat rate of the legs. The impermeable suit worn during C2 led to a greater physiological strain compared to the plastic film worn during C1 even with local ventilation under the impermeable garment. As expected, limiting sweat evaporation led to an increase in physiological strain. Microclimate ventilation at a rate of 40 l.min-1 was not sufficient to allow total heat dissipation but allowed 60-min exercise in a warm environment to be completed without excessive heat accumulation. It would appear that ventilation of the trunk locally was the best solution because of the smaller increase in skin temperature and higher sweating capacity of the trunk.

Local sweating responses during recovery sleep after sleep deprivation in humans.

Changes in the central control of sweating were investigated in five sleep-deprived subjects (kept awake for 40 h) during their recovery sleep under warm ambient conditions [operative temperature (T(o)) was either 35 or 38 degrees C]. Oesophageal (T(oes)) and mean skin (Tsk) temperatures, chest sweat rate (msw,ch), and concomitant electro-encephalographic data were recorded. Throughout the night at 35 or 38 degrees C T(o), msw,ch changes were measured at a constant local chest skin temperature (Tch) of 35.5 degrees C. The results showed that body temperatures (T(oes) and Tsk) of sleep-deprived subjects were influenced by thermal and hypnogogic conditions. The msw,ch levels correlated positively with T(oes) in the subjects studied during sleep stage 1-2 (light sleep: LS), sleep stage 3-4 (slow wave sleep: SWS) and rapid eye movement (REM) sleep. Contrary to what has been reported in normal sleep, firstly, the T(oes) threshold for sweating onset differed between REM sleep and both LS and SWS, and, secondly, the slopes of the msw,ch versus T(oes) relationships were unchanged between REM and non-REM (i.e. LS or SWS) sleep. The changes observed after sleep deprivation were hypothesized to be due to alterations in the functioning of the central nervous system controller.

Qualitative assessment of thermal and evaporative adjustments of human scrotal skin in response to heat stress.

To study scrotal thermoregulation and its efficacy to work against heat accumulation, five subjects were exposed to four experimental conditions under which core and skin temperatures and sweat evaporative responses of various skin surfaces--chest, abdomen and scrotum--were compared. The temperature response of the scrotal area exhibited the largest inertia, and this observation is likely to be the consequence of heat exchange via the vascularization of testes and scrotum which is more efficient than in other parts of the body in limiting local heat storage, thus alleviating heat stress of the testis. The pulsatile nature and the synchronous pattern of the scrotal evaporative heat loss indicate that scrotal sweating takes place, although the gradient response appeared to be less marked than elsewhere in the body. Relatively low and inert scrotal temperature can partly explain this poor local drive for sweating.

Regulation of local sweating in sleep-deprived exercising humans.

Thermoregulatory sweating [total body (msw,b), chest (msw,c) and thigh (msw,t) sweating], body temperatures [oesophageal (T(oes)) and mean skin temperature (Tsk)] and heart rate were investigated in five sleep-deprived subjects (kept awake for 27 h) while exercising on a cycle (45 min at approximately 50% maximal oxygen consumption) in moderate heat (T(air) and T(wall) at 35 degrees C). The msw,c and msw,t were measured under local thermal clamp (Tsk,l), set at 35.5 degrees C. After sleep deprivation, neither the levels of body temperatures (T(oes), Tsk) nor the levels of msw,b, msw,c or msw,t differed from control at rest or during exercise steady state. During the transient phase of exercise (when Tsk and Tsk,l were unvarying), the msw,c and msw,t changes were positively correlated with those of T(oes). The slopes of the msw,c versus T(oes) or msw,t versus T(oes) relationships remained unchanged between control and sleep-loss experiments. Thus the slopes of the local sweating versus T(oes) relationships (msw,c and msw,t sweating data pooled which reached 1.05 (SEM 0.14) mg.cm-2.min-1.degree C-1 and 1.14 (SEM 0.18) mg.cm-2.min-1.degree C-1 before and after sleep deprivation) respectively did not differ. However, in our experiment, sleep deprivation significantly increased the T(oes) threshold for the onset of both msw,c and msw,t (+0.3 degrees C, P < 0.001). From our investigations it would seem that the delayed core temperature for sweating onset in sleep-deprived humans, while exercising moderately in the heat, is likely to have been due to alterations occurring at the central level.

Thermal and sweating responses in normal and atopic subjects under internal and moderate external heat stress.

To compare the thermoregulatory responses of normal subjects and patients with atopic dermatitis, the effect of exercise under moderate heat stress was examined in two groups of subjects. Each group of eight subjects (controls or clinical atopics) underwent a 90-min experiment after being equipped with probes for measurement of core and skin temperatures, heart rate and overall and local sweating rates. Sweat surface tension was determined from sweat collection made at the end of the session. The experimental procedure was as follows: 30 min rest at thermoneutrality, 30 min cycling at 90 W at 36 degrees C, followed by 30 min recovery sitting at rest at 36 degrees C on the cycloergometer. None of the registered variables differed significantly between the normal and atopic subjects except for variations in mean skin temperature, core-to-skin temperature difference and sweat surface tension. Since local sweating on non-affected skin under a controlled thermal clamp was not altered by atopy, it can be concluded that the thermoregulatory modifications under heat stress is of vasomotor origin, the benefit of which, in terms of heat dissipation capacity, remains uncertain. There may be alterations in the constituents of sweat, but not in its excretion rate. Local, rather than central, factors are probably involved in this qualitative change, which remains to be investigated.

Sleep changes in fasting rats after chronic glycerol feeding.

Species which do not enter torpor during fasting and which were efficiently able to spare their body proteins during the first two phases of fasting (which are commonly comprised of 3 successive phases) also increase their daily amount of slow-wave sleep (SWS) during the first two phases. Since in fasting animals the ability to spare proteins was reported to be improved when they were previously fed with a diet enriched with glycerol, it was supposed that, after such a diet, food-deprived rats would increase their daily quota of SWS. In addition, the tolerance to food deprivation, defined as the time elapsed to reach the end of phase II, should also be improved since this tolerance is known to be critically modulated by protein utilization. The daily proportions of wakefulness (W), SWS and paradoxical sleep (PS) were thus studied in Wistar rats after 16 weeks of feeding (i.e., when they were 27 weeks old) with an enriched glycerol diet. These daily W and sleep state proportions were then evaluated until the middle of fasting phase II (MII), i.e., when protein catabolism in the rat appears to be at its lowest level. The rats were able to tolerate more than 5 weeks of food deprivation, which represented an increase of 123% of the fasting tolerance previously reported in rats of the same age but which were fed normally before fasting onset. At MII the daily proportion of SWS was significantly (vs. fed state, p less than 0.01) increased (due to an increase in the daily mean episode duration), at the expense of W (due to a lowering in the daily occurrence of W episodes).(ABSTRACT TRUNCATED AT 250 WORDS)

Leg skin temperature and thigh sweat output: possible central influence of local thermal inputs.

To demonstrate whether or not the skin temperature of one lower limb can have an influence on the sweat rate of the contralateral leg, the two legs of five subjects were exposed inside leg-chambers to specific local thermal conditions while sweat rates were measured on both limbs. Three experiments (C I, II, III) of 3 h were carried out: each included two phases A and B. During A, the right leg was not ventilated, while the left leg was (C I) or was not (C II-III) ventilated. During B, the legs were either removed from the leg-chambers (C I) or ventilated inside the chambers at differently controlled levels of leg skin temperature (C II-III). At all times, sweat capsules on both legs measured the sweat rates of local areas of the thigh which were also temperature-controlled. Results showed that, at constant or slightly increased mean skin and core temperatures, the sweat output of one leg could be decreased at constant (C II) or higher local skin temperature (C III) probably due to a decrease in the temperature of the opposite leg. This finding is interpreted as a consequence of a central negative effect, originating from contralateral thermal inputs.

Temperature and sweating responses in one-legged and two-legged exercise.

In looking at the thermoregulatory responses resulting from symmetrical or asymmetrical exercise, this paper has focused on the effect of local skin temperature (Tsk,local) on local sweat rates (msw,local) during one-legged (W1) and two-legged (W2) exercise on an ergocycle. Five subjects underwent four 3-h tests at 36 degrees C, each consisting of six 25-min exercise periods alternating with 5-min rest periods. The subjects performed W1 and W2 at 45 and 90 W, respectively, either dehydrated or rehydrated. Body temperatures and total sweat rate were measured as well as four msw,local (on chest and thighs), assessed from sweat capsules under which Tsk,local was maintained at predetermined levels (37.0 degrees C and 35.5 degrees C). The combinations of Tsk,local levels, capsule locations, exercise intensity and hydration level chosen in our protocol led to the following results. The hydration level affected rectal temperature but not total or msw,local. No specific effect of muscle activity was found; msw,local on thighs of resting and working legs were similar. The msw,local were only influenced by exercise intensity, msw,local being more elevated during the higher intensity. No significant effect of Tsk,local on msw,local was found, whatever the experimental condition and/or the location. It was concluded that local thermal effects on msw,local could have been masked by the strong central drive for sweating which has been found to exist in subjects exercising in a warm environment.

Physiological effects of dehydration and rehydration with water and acidic or neutral carbohydrate electrolyte solutions.

Five healthy young men exercised on an ergocycle for six 25-min periods separated by 5-min rest intervals in a warm dry environment (36 degrees C). After 1 h of exercise without fluid intake, the subjects continued to be dehydrated or were rehydrated either with water (W) or with isosmotic electrolyte carbohydrate solutions, either acidic (AISO) or close to neutrality (NISO). The average amount of the fluid ingested progressively every 10 min (120 ml) at 20 degrees C was calculated so as to compensate for 80% of the whole body water loss due to exercise in the heat. Dehydration associated with hyperosmotic hypovolaemia elicited large increases in heart rate (HR), and in rectal temperature (Tre), while no decrease was found in either whole body or local sweat rates. Rehydration with water significantly reduced the observed disturbances, except for plasma osmolality and Na+ concentration which were significantly lower than normal. With both AISO and NISO there was no plasma volume reduction and osmolality increase. Although a plasma volume expansion was induced by NISO ingestion, the cardiac cost was not improved, as reflected by the absence of a decrease in HR. With NISO, sweating was not enhanced and Tre tended to remain higher. It is concluded that efficient rehydration requires the avoidance of plasma volume expansion at the expense of interstitial and intracellular rehydration. During rehydration by oral ingestion of fluid, the pH of the drink may be an important factor; its effect remains unclear, however.

Growth hormone and prolactin response to rehydration during exercise: effect of water and carbohydrate solutions.

The effect of progressive rehydration with either water or a carbohydrate solution on the plasma growth hormone (GH) and prolactin (PRL) response to exercise was examined together with plasma somatostatin. Five subjects underwent four 3-h experimental sessions at 36 degrees C in which 25-min exercise periods alternated with 5-min rest periods. The sessions were conducted without fluid replacement (DH) or under rehydration with either water or isosmotic carbohydrate solutions AISO (acid) or NISO (neutral). The fluid was given every 10 min after the 1st h of exercise. Plasma GH increased significantly (p less than 0.01) under DH after 2 and 3 h of exercise; this increase was prevented by rehydration with water, AISO and NISO. Plasma glucose was significantly higher following AISO and NISO rehydration compared with DH. This possibly influenced the GH response, but there was no difference between plasma glucose levels under DH and water rehydration at any time. The solutions tended to attenuate the increase in heart rate, rectal temperature and plasma cortisol, suggesting that the lack of GH response under rehydration conditions is a result of decreasing physiological stress levels. The GH response could not be explained by plasma somatostatin, which tended to decline in all sessions. Plasma PRL did not increase in any of the sessions, confirming that exercise without rehydration is a more potent stimulator of GH than of PRL. It is concluded that progressive rehydration with water is sufficient to prevent the exercise-induced increase in plasma GH.