Arianna Novati

Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation

Sleep is important for brain function and cognitive performance. Sleep deprivation (SD) may affect subsequent learning capacity and ability to form new memories, particularly in the case of hippocampus‐dependent tasks. In the present study we examined whether SD for 6 or 12 h during the normal resting phase prior to learning affects hippocampus‐dependent working memory in mice. In addition, we determined effects of SD on hippocampal glutamate α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and their regulatory pathways, which are crucially involved in working memory. After 12 h SD, but not yet after 6 h, spatial working memory in a novel arm recognition task was significantly impaired. This deficit was not likely due to stress as corticosterone levels after SD were not significantly different between groups. In parallel with the change in cognitive function, we found that 12 h SD significantly reduced hippocampal AMPA receptor phosphorylation at the GluR1‐S845 site, which is important for incorporation of the receptors into the membrane. SD did not affect protein levels of cyclic‐AMP‐dependent protein kinase A (PKA) or phosphatase calcineurin (CaN), which regulate GluR1 phosphorylation. However, SD did reduce the expression of the scaffolding molecule A‐kinase anchoring protein 150 (AKAP150), which binds and partly controls the actions of PKA and CaN. In conclusion, a relatively short SD during the normal resting phase may affect spatial working memory in mice by reducing hippocampal AMPA receptor function through a change in AKAP150 levels. Together, these findings provide further insight into the possible mechanism of SD‐induced hippocampal dysfunction and memory impairment.

Maternal separation decreases adult hippocampal cell proliferation and impairs cognitive performance but has little effect on stress sensitivity and anxiety in adult Wistar rats

Stressful events during childhood are thought to increase the risk for the development of adult psychopathology. A widely used animal model for early life stress is maternal separation (MS), which is thought to affect development and cause alterations in neuroendocrine stress reactivity and emotionality lasting into adulthood. However, results obtained with this paradigm are inconsistent. Here we investigated whether this variation may be related to the type of stressor or the tests used to assess adult stress sensitivity and behavioral performance. Rat pups were exposed to a 3h daily MS protocol during postnatal weeks 1-2. In adulthood, animals were subjected to a wide variety of stressors and tests to obtain a better view on the effects of MS on adult hypothalamic-pituitary-adrenal (HPA) axis regulation, anxiety-like behavior, social interaction and cognition. Also, the influence of MS on adult hippocampal neurogenesis was studied because it might underlie changes in neuroendocrine regulation and behavioral performance. The results show that, independent of the nature of the stressor, MS did not affect the neuroendocrine response. MS did not influence anxiety-like behavior, explorative behavior and social interaction, but did affect cognitive function in an object recognition task. The amount of new born cells in the hippocampal dentate gyrus was significantly decreased in MS animals; yet, cell differentiation and survival were not altered. In conclusion, while interfering with the mother-infant relationship early in life did affect some aspects of adult neuroplasticity and cognitive function, it did not lead to permanent changes in stress sensitivity and emotionality.

Chronic sleep restriction causes a decrease in hippocampal volume in adolescent rats, which is not explained by changes in glucocorticoid levels or neurogenesis

Sleep loss strongly affects brain function and may even predispose susceptible individuals to psychiatric disorders. Since a recurrent lack of sleep frequently occurs during adolescence, it has been implicated in the rise in depression incidence during this particular period of life. One mechanism through which sleep loss may contribute to depressive symptomatology is by affecting hippocampal function. In this study, we examined the effects of sleep loss on hippocampal integrity at young age by subjecting adolescent male rats to chronic sleep restriction (SR) for 1 month from postnatal day 30 to 61. They were placed in slowly rotating drums for 20 h per day and were allowed 4 h of rest per day at the beginning of the light phase. Anxiety was measured using an open field and elevated plus maze test, while saccharine preference was used as an indication of anhedonia. All tests were performed after 1 and 4 weeks of SR. We further studied effects of SR on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure hippocampal volume and neurogenesis. Behavior of the SR animals was not affected, except for a transient suppression of saccharine preference after 1 week of SR. Hippocampal volume was significantly reduced in SR rats compared to home cage and forced activity controls. This volume reduction was not paralleled by reduced levels of hippocampal neurogenesis and could neither be explained by elevated levels of glucocorticoids. Thus, our results indicate that insufficient sleep may be a causal factor in the reductions of hippocampal volume that have been reported in human sleep disorders and mood disorders. Since changes in HPA activity or neurogenesis are not causally implicated, sleep disturbance may affect hippocampal volume by other, possibly more direct mechanisms.

Metabolic consequences of chronic sleep restriction in rats: Changes in body weight regulation and energy expenditure

Epidemiological studies have shown an association between short or disrupted sleep and an increased risk to develop obesity. In animal studies, however, sleep restriction leads to an attenuation of weight gain that cannot be explained by changes in energy intake. In the present study, we assessed whether the attenuated weight gain under conditions of restricted sleep is a consequence of an overall increase in energy expenditure. Adult male rats were subjected to a schedule of chronic sleep restriction (SR) for 8 days with a 4h window of unrestricted rest per day. Electroencephalogram and electromyogram recordings were performed to quantify the effect of the sleep restriction schedule on sleep-wake patterns. In a separate experiment, we measured sleep restriction-induced changes in body weight, food intake, and regulatory hormones such as glucose, insulin, leptin and corticosterone. To investigate whether a change in energy expenditure underlies the attenuation of weight gain, energy expenditure was measured by the doubly labeled water method from day 5 until day 8 of the SR protocol. Results show a clear attenuation of weight gain during sleep restriction but no change in food intake. Baseline plasma glucose, insulin and leptin levels are decreased after sleep restriction which presumably reflects the nutritional status of the rats. The daily energy expenditure during SR was significantly increased compared to control rats. Together, we conclude that the attenuation of body weight gain in sleep restricted rats is explained by an overall increase in energy expenditure together with an unaltered energy intake.

Chronic partial sleep deprivation reduces brain sensitivity to glutamate N-methyl-d-aspartate receptor-mediated neurotoxicity

It has been hypothesized that insufficient sleep may compromise neuronal function and contribute to neurodegenerative processes. While sleep loss by itself may not lead to cell death directly, it may affect the sensitivity to a subsequent neurodegenerative insult. Here we examined the effects of chronic sleep restriction (SR) on the vulnerability of the brain to N‐methyl‐d‐aspartate (NMDA)‐induced excitotoxicity. Animals were kept awake 20 h per day and were only allowed to rest during the first 4 h of the light phase, i.e. their normal circadian resting phase. After 30 days of SR all rats received a unilateral injection with a neurotoxic dose of NMDA into the nucleus basalis magnocellularis (NBM). Brains were collected for assessment of damage. In the intact non‐injected hemisphere, the number of cholinergic cells in the NBM and the density of their projections in the cortex were not affected by SR. In the injected hemisphere, NMDA caused a significant loss of cholinergic NBM cells and cortical fibres in all animals. However, the loss of cholinergic cells was attenuated in the SR group as compared with the controls. These data suggest that, if anything, SR reduces the sensitivity to a subsequent excitotoxic insult. Chronic SR may constitute a mild threat to the brain that does not lead to neurodegeneration by itself but prepares the brain for subsequent neurotoxic challenges. These results do not support the hypothesis that sleep loss increases the sensitivity to neurodegenerative processes.

Restricted and disrupted sleep : changes in HPA axis regulation and stress reactivity

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

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