Sleep deprivation under sustained hypoxia protects against oxidative stress

We previously showed that total sleep deprivation increased antioxidant responses in several rat brain regions. We also reported that chronic hypoxia enhanced antioxidant responses and increased oxidative stress in rat cerebellum and pons, relative to normoxic conditions. In the current study, we examined the interaction between these two parameters (sleep and hypoxia). We exposed rats to total sleep deprivation under sustained hypoxia (SDSH) and compared changes in antioxidant responses and oxidative stress markers in the neocortex, hippocampus, brainstem, and cerebellum to those in control animals left undisturbed under either sustained hypoxia (UCSH) or normoxia (UCN). We measured changes in total nitrite levels as an indicator of nitric oxide (NO) production, superoxide dismutase (SOD) activity and total glutathione (GSHt) levels as markers of antioxidant responses, and levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyls as signs of lipid and protein oxidation products, respectively. We found that acute (6h) SDSH increased NO production in the hippocampus and increased GSHt levels in the neocortex, brainstem, and cerebellum while decreasing hippocampal lipid oxidation. Additionally, we observed increased hexokinase activity in the neocortex of SDSH rats compared to UCSH rats, suggesting that elevated glucose metabolism may be one potential source of the enhanced free radicals produced in this brain region. We conclude that short-term insomnia under hypoxia may serve as an adaptive response to prevent oxidative stress.     

Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones

Sleep deprivation (SD) can suppress cell proliferation in the hippocampal dentate gyrus of adult male rodents, suggesting that sleep may contribute to hippocampal functions by promoting neurogenesis. However, suppression of cell proliferation in rats by the platform-over-water SD method has been attributed to elevated corticosterone (Cort), a potent inhibitor of cell proliferation and nonspecific correlate of this procedure. We report here results that do not support this conclusion. Intact and adrenalectomized (ADX) male rats were subjected to a 96-h SD using multiple- and single-platform methods. New cells were identified by immunoreactivity for 5-bromo-2'-deoxyuridine (BrdU) or Ki67 and new neurons by immunoreactivity for BrdU and doublecortin. EEG recordings confirmed a 95% deprivation of rapid eye movement (REM) sleep and a 40% decrease of non-REM sleep. Cell proliferation in the dentate gyrus was suppressed by up to 50% in sleep-deprived rats relative to apparatus control or home cage control rats. This effect was also observed in ADX rats receiving continuous low-dose Cort replacement via subcutaneous minipumps but not in ADX rats receiving Cort replacement via drinking water. In these latter rats, Cort intake via water was reduced by 60% during SD; upregulation of cell proliferation by reduced Cort intake may obscure inhibitory effects of sleep loss on cell proliferation. SD had no effect on the percentage of new cells expressing a neuronal phenotype. These results demonstrate that the Cort replacement method is critical for detecting an effect of SD on cell proliferation and support a significant role for sleep in adult neurogenesis.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Sleep and epilepsy

Sleep and Biological Rhythms - This review article aims to describe the strong association between sleep and epilepsy. Sleep disturbance or sleep disorders are frequently observed comorbid...     

Sleep and pregnancy

Sleep disturbances are frequent during pregnancy and are currently regarded as one of the most important factors determining pregnancy outcome. Detailed research of sleep features during pregnancy is obviously essential. In the present review recent data concerning changes in sleep structure and regulation in pregnant women and rats - main subjects of experimental sleep research, are given, including surmised mechanisms underlying such changes. The importance of women's sleep integrity preservation during pregnancy for the viability and normal development of the fetus is emphasized and possible ways of pathological influence of sleep disorders during this period are discussed.     

Sleep impairments in healthy seniors: roles of stress, cortisol, and interleukin-1 beta

Study Objectives: Increased stress responsivity and a longer-lasting glucocorticoid increase are common findings in aging studies. Increased cortisol levels at the circadian nadir also accompany aging. We used 24h free urine cortisol to assess these age changes in healthy seniors. We hypothesized that free cortisol levels would explain individual differences in age-related sleep impairments. Design: The study compared sleep, cortisol, and sleep-cortisol correlations under baseline and “stress” conditions in men and women. Setting: Subjects were studied in the General Clinical Research Center under baseline conditions and a mildly stressful procedure (24h indwelling intravenous catheter placement). Participants: Eighty-eight healthy, nonobese subjects (60 women and 28 men) from a large study of successful aging participated in the study. Mean ages were 70.6 (±6.2) and 72.3 (±5.7) years for women and men, respectively. Measurements: The 24h urines were collected for cortisol assay (radioimmunoassay [RIA]); blood was sampled at three diurnal time points for assay (enzyme-linked immunosorbent assay [ELISA]) of interleukin-1 (IL-1) beta; sleep architecture and sleep electroencephalograms (EEGs) were analyzed (after an adaptation and screening night) on baseline and stress nights via polysomnography and EEG power spectral analysis. Results: Healthy older women and men with higher levels of free cortisol (24h urine level) under a mild stress condition had impaired sleep (lower sleep efficiency; fewer minutes of stages 2, 3, and 4 sleep; more EEG beta activity during non-rapid eye movement sleep [NREM] sleep). Similar results were obtained when stress reactivity measures were used (cortisol and sleep values adjusted for baseline values), but not when baseline values alone were used. Gender differences were apparent: Men had higher levels of free urine cortisol in both baseline and mild stress conditions. Cortisol and sleep correlated most strongly in men; cortisol stress response levels explained 36% of the variance in NREM sleep stress responses. In women, but not men, higher cortisol was also associated with earlier time of arising and less REM sleep. Higher cortisol response to stress was associated with increased circulating levels of IL-1β, explaining 24% of the variance in a subset of women. Conclusion: These results indicate that free cortisol (as indexed by 24h urine values) can index responses to mild stress in healthy senior adults, revealing functional correlations (impaired sleep, earlier times of arising, more EEG beta activity during sleep, more IL-1β) and gender differences. (Chronobiology International, 17(3), 391-404, 2000)     

Dreams and Dreamless Sleep

Dreamless sleep, as subjective experience, is mentioned primarily within Hindu and Buddhist contexts. In the Upanishads, dreamless sleep is presented for the most part as objectless consciousness. Tibetan Buddhists speak of dreamless sleep in terms of a progression of visual experiences consisting of darkness and light. Contemporary discussions of dreaming, unless concerned with Eastern religion or philosophy, do not tend to mention dreamless sleep. For some writers today, dreaming includes all subjective experience during sleep, leaving no room for an experience of dreamless sleep. Some writers describe dreaming as a simulation of waking life. Since not all experience during sleep is simulation, this concept allows for experiences during sleep that may be understood to be other than dreaming. The writer finds it useful to consider simulation as the determining characteristic of dreaming and finds certain other sleep experiences then that are best considered to be dreamless.     

Plasma Trytophan and Sleep

Free, bound, and total plasma tryptophan (F.P.T., B.P.T., and T.P.T.) levels have been measured throughout the night in six young female volunteers. All-night polygraphic sleep recordings were also made. No direct temporal relationship was found between plasma tryptophan levels and specific sleep stages. The mean F.P.T. levels, however, were found to have a positive correlation with rapid-eye-movement (R.E.M.) sleep and a negative correlation with non-R.E.M. sleep. An inverse relationship existed between the F.P.T. and B.P.T. levels. There appeared to be a diurnal variation in F.P.T. levels, with high readings in the first half of the night.     

The UPR and the Anti-oxidant Response: Relevance to Sleep and Sleep Loss

Oxidative stress has been linked to various physiological and pathological processes such as aging and neurological disorders. Recent evidence has now implicated a role for oxidative stress in sleep and sleep loss. Studies suggest that wakefulness results in an oxidative burden and sleep provides a protective mechanism against these harmful effects. Prolonged wakefulness/sleep deprivation activates an adaptive stress pathway termed the unfolded protein response (UPR), which temporarily guards against the deleterious consequences of reactive oxygen species. The UPR affects the function of the endoplasmic reticulum, which is the site for integral and secretory membrane processing and folding. Several downstream effectors of the UPR operate in an antioxidant capacity to reduce the load of these toxic species; a process that may be important in delaying the progression of neurodegenerative diseases. This review will highlight the molecular components of the UPR that ameliorate the accumulation of oxidative stress and may therefore provide potential therapeutic targets.