Viktor Roman

Hippocampal cell proliferation across the day: Increase by running wheel activity, but no effect of sleep and wakefulness

The present study investigated whether proliferation of hippocampal progenitors is subject to circadian modulation. Mice were perfused using 3h intervals throughout the light-dark cycle and brains were stained for Ki-67. Since Ki-67 is not expressed during the G0 phase of the cell cycle, we expected a decline in Ki-67 expression at the moment cells synchronously exit the cell cycle. However, despite the fact that various hippocampal factors fluctuate across the day, the number of dividing cells remained constant. In a second experiment, we studied whether disturbance of normal sleep affected the stable rate in cell proliferation. Our data show that 12h of sleep deprivation during the light phase did not influence proliferating cell number. A third experiment investigated whether physical activity, a condition known to enhance hippocampal cell proliferation, caused an elevation of the steady baseline number of proliferating progenitors, or a peak directly following the active phase of the animals. Mice were housed with a running wheel for 9 days. On the last day, animals were sacrificed either directly before or directly after the active phase. Exercise significantly promoted cell proliferation and this effect appeared to be strongest directly after the active period and to disappear during the resting phase. Our data suggest that hippocampal cell proliferation is not synchronized under basal conditions and is unchanged by sleep deprivation. However, running affected cell proliferation differentially at two times of day. These data demonstrate that the steady rate in cell proliferation is not indispensable, but can be changed by behavioral activity.

Resveratrol preserves cerebrovascular density and cognitive function in aging mice

Resveratrol, a natural polyphenol abundant in grapes and red wine, has been reported to exert numerous beneficial health effects. Among others, acute neuroprotective effects of resveratrol have been described in several models of neurodegeneration, both in vitro and in vivo. In the present study we examined the neuroprotective effects of long-term dietary supplementation with resveratrol in mice on behavioral, neurochemical and cerebrovascular level. We report a preserved cognitive function in resveratrol-treated aging mice, as shown by an enhanced acquisition of a spatial Y-maze task. This was paralleled by a higher microvascular density and a lower number of microvascular abnormalities in comparison to aging non-treated control animals. We found no effects of resveratrol supplementation on cholinergic cell number or fiber density. The present findings support the hypothesis that resveratrol exerts beneficial effects on the brain by maintaining cerebrovascular health. Via this mechanism resveratrol can contribute to the preservation of cognitive function during aging.

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.

Repetitive stimulation of adenosine A1 receptors in vivo: Changes in receptor numbers, G-proteins and A1 receptor agonist-induced hypothermia

Adenosine is an important neuromodulator and neuroprotective molecule, which is produced in the brain as a function of neuronal activity, coupling energy expenditure to energy supply. Under conditions of increased need and reduced availability of energy, including hypoxia and prolonged wakefulness, there is an increase in adenosine turnover and adenosine receptor stimulation. The aim of the present study was to examine how repetitive adenosine receptor stimulation affects receptor function and adenosinergic signaling in the brain. Adult male Wistar rats received daily intraperitoneal injections of the adenosine A1 receptor agonist N(6)-cyclopentyladenosine (CPA; 0.25 mg/kg; once per day) and effects on adenosine signaling were established with receptor and G-protein autoradiography. Injections of CPA for 5 consecutive days caused a significant decrease in adenosine A1 receptor numbers in the hippocampus and somatosensory cortex. In contrast, while the amount of adenosine A1 receptor-activated G-proteins was not affected in most regions, a significant increase was found in the somatosensory cortex. On the level of physiological output, CPA-induced hypothermia was significantly attenuated, suggesting a functional desensitization of the A1 receptor system. Taken together, the present findings suggest that repetitive stimulation of the A1 receptors can affect elements of the adenosinergic signaling cascade in the rat brain in a region-specific manner.

TGFα and AVP in the mouse suprachiasmatic nucleus: Anatomical relationship and daily profiles

Daily rhythms in behavior and physiology are under control of the suprachiasmatic nucleus (SCN), the main mammalian circadian pacemaker located in the hypothalamus. The SCN communicates with the rest of the brain via various output systems. The aim of the present study was to determine the neuroanatomical and temporal relationship between two output systems, arginine-vasopressin (AVP) and transforming growth factor alpha (TGFalpha), in the mouse SCN. TGFalpha-positive cells were found throughout the SCN, but more abundantly in the core than the shell area, while AVP was predominantly found in the shell. Fluorescent double labeling revealed a total lack of co-expression for the two proteins in SCN cells. The circadian profile, studied by way of optical density in immunostaining at 3 h intervals, showed peak values for AVP shortly after the LD transitions. Immunoreactivity for TGFalpha was highly variable, especially at time points before the LD transitions. In addition, strong lateralization in TGFalpha immunostaining in the SCN was found in some individuals. Daily fluctuations in the paraventricular nucleus were absent for TGFalpha, and only weakly present for AVP. The main conclusion derived from this study is that these two output systems of the biological clock are anatomically separated with different daily profiles in expression.

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