Paula Ayako Tiba

Hormonal and Behavioural Responses of Paradoxical Sleep‐Deprived Rats to the Elevated Plus Maze

Activation of the hypothalamic‐pituitary‐adrenal (HPA) axis is observed immediately after 96 h of paradoxical sleep (PS) deprivation. However, when individually or group PS‐deprived rats are challenged with a mild stressor, they exhibit a facilitation of the corticosterone response, and a faster return to basal levels than control rats. Because the housing condition influences coping behaviour, we tested whether the type of PS deprivation (individually or in group) influenced anxiety‐like behaviour in the elevated plus‐maze and the accompanying adrenocorticotropin (ACTH) and corticosterone responses. Individually (I‐DEP) or group deprived (G‐DEP) rats and their appropriate control groups were either killed immediately after 96 h of sleep deprivation (time‐point 0 or ‘basal’) or exposed to a 5‐min test on the elevated plus maze and sampled 5, 20 or 60 min after test onset. Control of I‐DEP rats showed reduced locomotor activity and augmented anxiety‐like behaviour, replicating the effects of social isolation. Although I‐DEP rats exhibited higher motor activity than cage control rats, these groups did not differ in regard to the percentage of entry and time spent in the open arms. G‐DEP rats, in turn, ambulated more, entered and remained longer in the open arms, exhibiting less anxiety‐like behaviour. PS‐deprived rats exhibited higher ACTH and corticosterone ‘basal’ secretion than control rats. For all groups, peak ACTH secretion was reached at the 5‐min time‐point, returning to unstressed basal levels 60 min after the test, except for G‐DEP rats, which showed a return at 20 min. Peak levels of corticosterone occurred at 5 min for PS‐deprived groups and at 20 min for control groups. G‐DEP rats showed a return to ‘basal’ unstressed levels at 20 min, whereas the I‐DEP and control groups did so at 60 min. A negative correlation between exploration in the open arms and hormone concentrations was observed. These data indicate that housing condition influences the subsequent behaviour of PS‐deprived rats in the EPM which, in turn, seems to determine the secretion profile of ACTH and corticosterone in response to the test.

Disruptions of the mother-infant relationship and stress-related behaviours: Altered corticosterone secretion does not explain everything

The hypothalamic-pituitary-adrenal (HPA) axis is the main neuroendocrine system of response to stress, and an imbalance of this systems activity is believed to be at the core of numerous psychiatric pathologies. During the neonatal period, the glucocorticoid response to stress is maintained at low levels by specific maternal behaviours, which is essential for proper brain development. Effective evaluation of the impact of increased secretion of corticosterone during an essentially anabolic developmental period on adulthood behaviour involved separation of the neonate from its mother for periods ranging from 3 to 24h. It has been shown that disinhibition of the stress response is achieved by such procedures. The pioneering studies by Seymour Levine set the stage for a prolific and promising field of study that may help neuroscientists unveil the neurobiological underpinnings of stress-related disorders. Based on a series of studies, we propose that maternal separation and maternal deprivation change stress-related behaviours, but that corticosterone seem to be only partially involved in these changes in adulthood. It appears that extra-hypothalamic corticotrophin-releasing factor and neurotransmitter systems may be the primary mediators of these behavioural outcomes.

Effects of brief and long maternal separations on the HPA axis activity and the performance of rats on context and tone fear conditioning

Previous studies show that early life events result in neurobehavioural alterations that may be either beneficial or detrimental to the stress response. Given the close relationship between corticosterone secretion and mnemonic processes, the purpose of the present study was to investigate the effects of brief (BMS, 15 min) and long maternal separations (LMS, 180 min) on memory tasks in adult rats, assessed by context and tone fear conditioning. At adulthood, males were evaluated for behavioural and hormonal reaction to the training environment, being tested for context fear conditioning; tone fear conditioning; and learning curve in the context fear conditioning, in which rats were daily re-exposed to the context, followed by a brief footshock and in the last day of the experiment (day 5) animals were exposed to the context. Corticosterone and ACTH plasma levels were determined in naïve rats (basal) or 5, 25 or 45 min after each test. Peak ACTH and corticosterone levels were similar among the groups after context fear conditioning; however, levels of CTL rats remained elevated for a longer time. In the learning curve of context fear conditioning, both BMS and LMS rats exhibited less freezing behaviour than CTL rats, without differences in hormone secretion. There was neither an association between activity of the HPA axis and performance on memory tasks nor different activational properties of the tasks on the HPA axis between BMS and LMS rats, i.e., both manipulations lead to similar performance in hippocampus-dependent and independent memory tasks.

Paradoxical sleep deprivation facilitates subsequent corticosterone response to a mild stressor in rats

The pituitary-adrenal responsiveness to a mild stressor was assessed in rats that were deprived of paradoxical sleep (PS) and in controls that were not deprived. Animals were either individually- or group-deprived for 96 h and hormone levels were assessed at 0, 5, 20 or 60 min after a saline injection+novelty and compared with rats which were not deprived. Both types of PS deprivation resulted in elevated adrenocorticotropin levels at 0 min, which peaked at 5 min in all animals. Individually-deprived rats exhibited the highest corticosterone (CORT) levels at 0 min. Peak levels were higher and occurred earlier in PS-deprived than in control rats (5 vs. 20 min, respectively). At 20 min, CORT levels had already returned to unstressed levels in PS-deprived rats, but not in control rats. These data indicate that PS deprivation induces facilitation of the adrenocortical response to a mild stressor, but do not suggest that PS deprivation changes the negative feedback sensitivity to CORT.

Repercussões imunológicas dos distúrbios do sono: o eixo hipotálamo-pituitária-adrenal como fator modulador

OBJECTIVE: To review the literature on the interaction between sleep and the immune system. METHOD: A search on Web of Science and Pubmed database including the keywords sleep, sleep deprivation, stress, hypothalamic-pituitary-adrenal axis, immune system, and autoimmune diseases. RESULTS: On Web of Science, 588 publications were retrieved; 61 references, more significant and closer to our objective, were used, including original articles and review papers. CONCLUSION: Sleep deprivation and immune system exert a bidirectional influence on each other. Since sleep deprivation is considered a stressor, inasmuch as it induces elevation of cortisol or corticosterone levels in humans and rodents, respectively, and given the well-known immunosuppressive effect of glucocorticoids, we propose that increased activation of the hypothalamic-pituitary-adrenal axis is a major mediator of the immune alterations observed in patients with insomnia or in sleep deprived subjects.

Long lasting alteration in REM sleep of female rats submitted to long maternal separation.

Early adverse experiences represent risk factors for the development of anxiety and mood disorders. Maternal separation can induce biobehavioral alterations in male rodents similar to those seen in depressed humans, such as hyperresponsiveness to stress and sleep disturbances. Nonetheless, no study has yet explored the effects of early life events on the relationship between stress and sleep in female rats. Whole litters of Wistar rats were submitted to brief- or long maternal separations (15 [BMS] or 180 min/day [LMS], from postnatal days 2-14) or kept undisturbed with their mothers (CTL). When adults, female rats were sleep-recorded for 22 h before (baseline) and after a 1 h exposure to cold stress (post-stress). Additional subsets of animals were sacrificed before, 1 or 3 h after the stressor for plasma corticosterone determination. No differences in baseline sleep were observed among the groups. Female rats submitted to LMS exhibited a significant increase of REM sleep on the night following a 1 h exposure to cold stress, whereas the sleep of BMS rats was barely altered by stress. All groups exhibited similar basal and stress-induced corticosterone levels. The present results are compared to a previous study performed in male rats, and corroborate that manipulations applied during infancy modify the expression of stress-induced sleep rebound.

Effects of early handling on basal and stress-induced sleep parameters in rats

Exposure of humans and animals to stressful events early in life leads to significant and often permanent behavioural, neuroendocrine and central alterations. Early handling consists of removing the litter from the nest for 15 min/day, from post-natal days 2 to 14 and results in lowered ACTH and corticosterone stress response and reduced anxiety-like and fear behaviours. Stress-induced sleep alterations usually consists of increased sleep time, known as sleep rebound. In the present study, basal and stress-induced sleep pattern of control non-manipulated (CTL) and early handled (EH) adult male rats was investigated. Sleep was evaluated by 21-h polysomnographic recordings (from 10:00 to 07:00 h of the next day) before and after a 1-h session of restraint stress. The results showed that in the first 3 h following stress, both CTL and EH animals exhibited an impairment of sleep, with a reduction of sleep efficiency, duration of slow wave sleep and of paradoxical sleep. On the contrary, time awake and awakening bouts were augmented in this period. Sleep rebound was observed mainly in the dark period of the light-dark cycle. Stress-induced sleep changes were similar between CTL and EH animals for most sleep parameters. However, EH animals exhibited more bouts of paradoxical sleep on the night following stress exposure and longer bouts of paradoxical sleep in the light period that followed restraint stress. These data indicate that stress-induced alterations of sleep in early handled animals are similar to that observed in control animals, except for some parameters related to paradoxical sleep.

Lithium prevents REM sleep deprivation-induced impairments on memory consolidation.

BACKGROUND Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. OBJECTIVE To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. DESIGN Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. SUBJECTS Wistar male rats weighing 300-400 g. RESULTS Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. CONCLUSION Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained.

High corticosterone after olfactory social stimuli in a rodent model of traumatic stress.

Posttraumatic stress disorder (PTSD) is characterized by recurrent recollections and avoidance of the traumatic event and general hyperarousal that affect some victims of life-threatening events. In addition to the important application of animal fear conditioning paradigms in psychobiological studies of the mnemonic aspect of PTSD, special attention should be devoted to the exaggerated emotional and hormonal reactions to unconditioned stimuli, hallmarks of PTSD. Overreacting to harmless stimuli that do not bear resemblance to learned threats may be the result of a process of fear sensitization, which is vastly maladaptive and may interfere with daily life. It is argued that fear sensitization can possibly underpin the emergence of unconditioned behavioral disturbances seen in PTSD. Social withdrawal is also seen in PTSD, and physiological reactions may exacerbate behavioral avoidance to social situations. In this regard, we have evaluated fear conditioning and several behavioral indexes of fear sensitization, characteristic of posttraumatic stress in rats. We hypothesized that exposure to novel social stimuli might be associated with high hormonal levels in rats previously submitted to an unpredictable and inescapable highly intense electric footshock, a model of severe stress. We found that, in addition to a robust contextual fear conditioning and a consistent behavioral overreactive state, the hormonal responsiveness to a socioenvironmental stimulus was also exacerbated in rats exposed to the traumatic stress, compared with control rats. Our data corroborate previous studies showing affective sequalae in PTSD animal models and provide additional information on physiological reactions associated with traumatic stress in rats.

Sleep deprivation affects memory formation and adaptation : studies on maze learning and reversal learning in mice

Objective: Does snoring during pregnancy influence development of pre-eclampsia?Method: Five hundred and three pregnant women were presented a questionnaire concerning snoring, daytime sleepiness a ...withdrawn O141 Sleep-wake cycle in ballet dancers M. GLOS, T. PENZEL, J. STRAUCH, C. THEOBALD and I. FIETZE Interdisciplinary Center of Sleep Medicine, Charité-Universitaetsmedizin Berlin, Berlin, Germany and Staatsballett Berlin, Berlin, Germany Introduction: Ballet dancers are top athletes and artists with extreme demands on their body and intellectual functions. In this group a normal work schedule on a weekly basis is absent and moreover, half of the week working days last until late evenings. Methods: We investigated the sleep-wake cycle over a period of three months prior to a premiere of a new performance by using actigraphy in 28 (17w, 11 m) ballet dancers (mean age 27 5 years, BMI 19 2) of the ‘‘Staatsballett Berlin’’, a big independent ballet institution of the three institutionalized opera houses in Berlin, Germany. Before starting the actigraphy recording (Actiwatch, Cambridge Neurotechnology Ltd, Cambridge, UK) which was accompanied by filling in activity diaries and sleep logs on a daily basis, a physical examination as well as a sleep medical examination and ambulatory polygraphy (Embletta PDS, Embla Systems, Broomfield, CO, USA) was performed. Results: Out of the 28 ballet dancers who were included, 24 of them completed the study after three months. Altogether we found a regular sleep-wake cycle but no circaseptan rhythm in this population. In addition a delayed sleep phase was predominant. In the course of three month the sleep efficacy (SE) was reduced significantly (82 to 77 percent, Po0.01) without changes in the amount of movements and total sleep time (TST) during the night. These findings were independent of the gender of the ballet dancers. The parameters SE and TST are generally lower than in the general age matched German population. These results were accompanied by diminished mental health scores (SF12 questionnaire) and diminished concentration capabilities (d2 test). Conclusion: The preparation time of a new performance in the course of three month caused additional stress in the investigated ballet dancers which was apparent in a diminished sleep quality. In order to guarantee a good status of health and the high degree of physical and mental capability a good management of rest and a activity is needed. As a consequence a dedicated room for rest has been installed at the opera for the ballet dancers. r 2008 European Sleep Research Society, JSR 17 (Suppl. 1), 1–271 Spotlight on Circadian Clock Works On and Off Stage 81