SLEEP

Roth,, Thomas;Drake, Christopher, L.

doi: 10.1093/sleep/27.7.1238pmid: N/A

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Gillette, Martha, U.

doi: 10.1093/sleep/27.7.1240pmid: N/A

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Arnulf,, Isabelle;Mignot,, Emmanuel

doi: 10.1093/sleep/27.7.1242pmid: N/A

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Buysse, Daniel, J.;Nofzinger, Eric, A.;Germain,, Anne;Meltzer, Carolyn, C.;Wood,, Annette;Ombao,, Hernando;Kupfer, David, J.;Moore, Robert, Y.

doi: 10.1093/sleep/27.7.1245pmid: 15586778

Abstract Study Objectives: The mechanisms that maintain wakefulness across the day, in the face in increasing sleep drive, are largely unknown. The goal of this pilot study was to examine regional relative brain glucose metabolism during morning and evening wakefulness in healthy humans. Design: [18F]-fluorodeoxyglucose positron emission tomography scans were conducted during quiet wakefulness in the morning and in the evening. Statistical parametric mapping was used to compare relative regional glucose metabolism during the 2 scans. Subjects also completed subjective ratings of alertness. Setting: University of Pittsburgh General Clinical Research Center and Positron Emission Tomography Facility. Patients or Participants: Thirteen healthy adults (10 women, 3 men; mean age, 37 years) Interventions: None. Measurements and Results: Relative regional glucose metabolism was significantly higher in the evening than in the morning in a large cluster of midline and brainstem structures. Volumes of interest centered on the pontine reticular formation, midbrain reticular formation, midbrain raphe, locus coeruleus, and posterior hypothalamus also showed higher relative metabolism in the evening than in the morning. Relative glucose metabolism was significantly lower in the evening than in the morning in clusters that included structures in the right temporal cortex and occipital lobe, including cuneus and medial occipital gyrus. Conclusions: Evening wakefulness is associated with increased relative metabolism in brainstem and hypothalamic arousal systems and decreased relative metabolism in posterior cortical regions. These patterns may reflect input from the circadian timing system to promote wakefulness, and/or the effects of increasing homeostatic sleep drive. alertness, circadian, brainstem, hypothalamus, positron emission tomography (PET) This content is only available as a PDF.

Ohayon, Maurice, M.;Carskadon, Mary, A.;Guilleminault,, Christian;Vitiello, Michael, V.

doi: 10.1093/sleep/27.7.1255pmid: 15586779

Abstract Objectives: The purposes of this study were to identify age-related changes in objectively recorded sleep patterns across the human life span in healthy individuals and to clarify whether sleep latency and percentages of stage 1, stage 2, and rapid eye movement (REM) sleep significantly change with age. Design: Review of literature of articles published between 1960 and 2003 in peer-reviewed journals and meta-analysis. Participants: 65 studies representing 3,577 subjects aged 5 years to 102 years. Measurement: The research reports included in this meta-analysis met the following criteria: (1) included nonclinical participants aged 5 years or older; (2) included measures of sleep characteristics by “all night” polysomnography or actigraphy on sleep latency, sleep efficiency, total sleep time, stage 1 sleep, stage 2 sleep, slow-wave sleep, REM sleep, REM latency, or minutes awake after sleep onset; (3) included numeric presentation of the data; and (4) were published between 1960 and 2003 in peer-reviewed journals. Results: In children and adolescents, total sleep time decreased with age only in studies performed on school days. Percentage of slow-wave sleep was significantly negatively correlated with age. Percentages of stage 2 and REM sleep significantly changed with age. In adults, total sleep time, sleep efficiency, percentage of slow-wave sleep, percentage of REM sleep, and REM latency all significantly decreased with age, while sleep latency, percentage of stage 1 sleep, percentage of stage 2 sleep, and wake after sleep onset significantly increased with age. However, only sleep efficiency continued to significantly decrease after 60 years of age. The magnitudes of the effect sizes noted changed depending on whether or not studied participants were screened for mental disorders, organic diseases, use of drug or alcohol, obstructive sleep apnea syndrome, or other sleep disorders. Conclusions: In adults, it appeared that sleep latency, percentages of stage 1 and stage 2 significantly increased with age while percentage of REM sleep decreased. However, effect sizes for the different sleep parameters were greatly modified by the quality of subject screening, diminishing or even masking age associations with different sleep parameters. The number of studies that examined the evolution of sleep parameters with age are scant among school-aged children, adolescents, and middle-aged adults. There are also very few studies that examined the effect of race on polysomnographic sleep parameters. meta-analysis, PSG, psychiatric disorders, sleep disorders, moderator analysis This content is only available as a PDF.

Gerashchenko,, Dmitry;Chou, Thomas, C.;Blanco-Centurion, Carlos, A.;Saper, Clifford, B.;Shiromani, Priyattam, J.

doi: 10.1093/sleep/27.7.1275pmid: 15586780

Abstract Study Objectives: Extensive evidence suggests that histaminergic neurons promote wakefulness. Histaminergic neurons are found exclusively in the tuberomammillary nucleus (TMN), and electrolytic lesions of the posterior hypothalamus, where the TMN resides, produce intense hypersomnolence. However, electrolytic lesions disrupt fibers of passage, and the effects of fiber-sparing, cell-specific TMN lesions on sleep and wakefulness are unknown. Hence, we placed cell-specific lesions in the TMN to determine its role in spontaneous wakefulness. Design: TMN neurons in rats are relatively resistant to excitotoxins. Hence, we ablated them using saporin conjugated to hypocretin 2, which ablates hypocretin receptor-bearing neurons such as TMN neurons. One to 2 weeks after bilateral injections of Hcrt2-SAP into Sprague-Dawley rats, we correlated loss of TMN neurons with changes in sleep. Setting: N/A Participants: N/A Interventions: N/A Measurements and Results: Four days after injections with hypocretin 2—saporin, the number of TMN neurons was markedly decreased, and most were lost after 12 days, as determined by immunohistochemistry for adenosine deaminase, a marker of TMN neurons. Nearby nonhistaminergic neurons were similarly ablated. Rats with an average 82.5% loss of TMN cells (determined 2 weeks after injection) did not have marked changes in total sleep amounts compared to saline-treated rats 1 or 2 weeks following the injection, except for a slight decrease in rapid eye movement sleep during the lights-on period for the first week only. The percentage of remaining TMN neurons positively correlated with the average duration of wake bouts during the lights-off period. Conclusion: The absence of gross changes in sleep after extensive loss of histaminergic neurons suggests that this system is not critical for spontaneous wakefulness. Histamine, tuberomammillary nucleus, hypocretin-2–saporin, lesions, rats This content is only available as a PDF.

Mavanji,, Vijayakumar;Ulloor,, Jagadish;Saha,, Subhash;Datta,, Subimal

doi: 10.1093/sleep/27.7.1282pmid: 15586781

Abstract Study Objectives: The aim of this study was to test the hypothesis that the activation of pontine (P)-wave generator is critical for the posttraining rapid eye movement (REM) sleep-dependent memory processing. Design: Ibotenic acid was microinjected (0.5 µg in 0.05 µL) into the functionally identified P-wave generator in order to destroy the cell bodies and thus to study the effects of their destruction upon waking-sleep states, Pwaves, and 2-way active avoidance memory. Setting: Sleep research laboratory at Boston University School of Medicine. Participants: Adult male Sprague-Dawley rats (N = 27). Interventions: Chronically implanted for recording polygraphic signs of sleep and bilateral guide tubes for the local microinjections into the Pwave generator. Measurements and Results: The ibotenic acid produced a small spherical area (≤ 0.35 mm in diameter) of nerve cell loss centered on the Pwave generator. Bilateral lesioning of the P-wave generator decreased Pwaves during REM sleep by > 95% without significantly changing the amounts of time spent in wake, slow-wave sleep, or REM sleep. In these P-wave generator-lesioned rats, acquisition of avoidance learning and posttraining wake-sleep changes were identical to those of the shamlesioned rats. However, in the test trials, after 6 hours of undisturbed sleep-wake, P-wave generator-lesioned rats had no retention of avoidance memory. Conclusions: These findings, for the first time, provide direct evidence that P-wave—generating cells are critical for normal REM sleep-dependent memory processing. This evidence supports our hypothesis that the P-wave generator in the brainstem may act as an on switch to provide activating input to forebrain structures for sleep-dependent memory processing. acquisition, brainstem, ibotenic acid lesion, learning and memory, P-wave generating cell, REM sleep, retention, 2-way active avoidance This content is only available as a PDF.

Garbarino,, Sergio;Mascialino,, Barbara;Penco, Maria, Antonietta;Squarcia,, Sandro;, De Carli, Fabrizio;Nobili,, Lino;Beelke,, Manolo;Cuomo,, Gianni;Ferrillo,, Franco

doi: 10.1093/sleep/27.7.1295pmid: 15586782

Easton,, Amy;Meerlo,, Peter;Bergmann,, Bernard;Turek, Fred, W.

doi: 10.1093/sleep/27.7.1307pmid: 15586783

Abstract Context: Sleep is regulated by circadian and homeostatic processes. The circadian pacemaker, located in the suprachiasmatic nuclei (SCN), regulates the timing and consolidation of the sleep-wake cycle, while a homeostatic mechanism governs the accumulation of sleep debt and sleep recovery. Recent studies using mice with deletions or mutations of circadian genes show that components of the circadian pacemaker can influence the total amount of baseline sleep and recovery from sleep deprivation, indicating a broader role for the SCN in sleep regulation. Objective: To further investigate the role of the circadian pacemaker in sleep regulation in mice, we recorded sleep in sham and SCN-lesioned mice under baseline conditions and following sleep deprivation. Results: Compared to sham controls, SCN-lesioned mice exhibited a decrease in sleep consolidation and a decrease in wakefulness during the dark phase. Following sleep deprivation, SCN-lesioned mice exhibited an attenuated increase in non-rapid eye movement sleep time but an increase in non-rapid eye movement sleep electroencephalographic delta power that was similar to that of the sham controls. Conclusions: These findings support the hypothesis that the SCN consolidate the sleep-wake cycle by generating a signal of arousal during the subjective night (ie. the active period), thereby having the capacity to alter baseline sleep amount. Although the SCN are not involved in sleep homeostasis as defined by the increase in electroencephalographic delta power after sleep deprivation, the SCN does play a central role in the regulation of sleep and wakefulness beyond just the timing of vigilance states. This content is only available as a PDF.

Miyamoto,, Masaomi;Nishikawa,, Hisao;Doken,, Yayoi;Hirai,, Keisuke;Uchikawa,, Osamu;Ohkawa,, Shigenori

doi: 10.1093/sleep/27.7.1319pmid: 15586784

Abstract Introduction: Ramelteon (TAK-375) is an MT1/MT2 receptor agonist being studied for the treatment of insomnia and circadian rhythm sleep disorders. We compared the behavioral effects of ramelteon and exogenous melatonin in freely moving cats. Methods: Ramelteon and melatonin were each suspended in a 0.5% (weight per volume) methylcellulose solution and administered orally to freely moving cats. In the control trial, each cat was given vehicle. Each dose of ramelteon or melatonin was compared with the vehicle control in a crossover design. Electroencephalogram, electromyogram, and electrooculogram recordings were assessed. Results: Ramelteon significantly decreased wakefulness at doses of 0.001, 0.01, and 0.1 mg/kg, increased slow-wave sleep at doses of 0.001, 0.01, and 0.1 mg/kg, and increased rapid eye movement sleep at a dose of 0.1 mg/kg, compared with the vehicle controls, as assessed by analysis of variance. The effects of ramelteon lasted for up to 6 hours when evaluated by reduction of wakefulness. Exogenous melatonin (0.01–1 mg/kg) significantly increased slow-wave sleep, but the effect was weaker than that of ramelteon and lasted for only 2 hours. The lowest doses of ramelteon (0.0001 mg/kg) and melatonin (0.001 mg/kg) had no significant effect on sleep-wakefulness stage. Conclusions: Ramelteon was more effective than exogenous melatonin in promoting and maintaining sleep in freely moving cats. Based on its unique mechanism of action, ramelteon should be studied further to evaluate its potential for the treatment of sleep disorders. ramelteon (TAK-375), melatonin, sleep, cat, electroencephalogram, slow-wave sleep, rapid eye movement, insomnia This content is only available as a PDF.