Roelina Hagewoud

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.

Sleep deprivation impairs contextual fear conditioning and attenuates subsequent behavioural, endocrine and neuronal responses

Sleep deprivation (SD) affects hippocampus‐dependent memory formation. Several studies in rodents have shown that brief SD immediately following a mild foot shock impairs consolidation of contextual fear memory as reflected in a reduced behavioural freezing response during re‐exposure to the shock context later. In the first part of this study, we examined whether this reduced freezing response is accompanied by an attenuated fear‐induced activation of the hypothalamic–pituitary–adrenal (HPA) axis. Results show that 6 h of SD immediately following the initial shock results in a diminished adrenal corticosterone (CORT) response upon re‐exposure to the shock context the next day. In the second part, we established whether the attenuated freezing response in SD animals is associated with reduced activation of relevant brain areas known to be involved in the retrieval and expression of fear memory. Immunohistochemical analysis of brain slices showed that the normal increase in phosphorylation of the transcription factor 3′,5′‐cyclic AMP response‐element binding protein (CREB) upon re‐exposure to the shock context was reduced in SD animals in the CA1 region of the hippocampus and in the amygdala. In conclusion, brief SD impairs the consolidation of contextual fear memory. Upon re‐exposure to the context, this is reflected in a diminished behavioural freezing response, an attenuated HPA axis response and a reduction of the normal increase of phosphorylated CREB expression in the hippocampus and amygdala.

Differential effects of chronic partial sleep deprivation and stress on serotonin-1A and muscarinic acetylcholine receptor sensitivity

Disrupted sleep and stress are often linked to each other, and considered as predisposing factors for psychopathologies such as depression. The depressed brain is associated with reduced serotonergic and enhanced cholinergic neurotransmission. In an earlier study, we showed that chronic sleep restriction by forced locomotion caused a gradual decrease in postsynaptic serotonin‐1A receptor sensitivity, whilst chronic forced activity alone, with sufficient sleep time, did not affect receptor sensitivity. The first aim of the present study was to examine whether the sleep loss‐induced change in receptor sensitivity is mediated by adrenal stress hormones. The results show that the serotonin‐1A receptor desensitization is independent of adrenal hormones as it still occurs in adrenalectomized rats. The second aim of the study was to establish the effects of sleep restriction on cholinergic muscarinic receptor sensitivity. While sleep restriction affected muscarinic receptor sensitivity only slightly, forced activity significantly hypersensitized the muscarinic receptors. This hypersensitization is because of the stressful nature of the forced activity protocol as it did not occur in adrenalectomized rats. Taken together, these data confirm that sleep restriction may desensitize the serotonin‐1A receptor system. This is not a generalized effect as sleep restriction did not affect the sensitivity of the muscarinic cholinergic receptor system, but the latter was hypersensitized by stress. Thus, chronic stress and sleep loss may, partly via different pathways, change the brain into a direction as it is seen in mood disorders.

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