Positive Correlations Between Cerebral Protein Synthesis Rates and Deep Sleep in <i>Macaca mulatta</i>

Nakanishi, Hajime; Sun, Yi; Nakamura, Reizo; Mori, Kentaro; Ito, Masanori; Suda, S.; Namba, Hiroki; Storch, Fredric I.; Dang, Thao P.; Mendelson, Wallace B.; Mishkin, Mortimer; Kennedy, Charles; Gillin, J. Christian; Smith, Carolyn Beebe; Sokoloff, Louis

doi:10.1111/j.1460-9568.1997.tb01397.x

Cited by 147 publications

(86 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…37), or by cellular efforts to limit protein turnover in a situation when little new protein is produced. These results in the fly brain are consistent with prior studies in the rat brain that showed a pattern of gene expression changes that would promote increased protein synthesis during sleep compared with wakefulness (15) and are compatible with earlier findings of increased cerebral protein synthesis during sleep compared with wakefulness in mammals (62,68).…”

Section: Discussionsupporting

confidence: 82%

Multiple mechanisms limit the duration of wakefulness in Drosophila brain

Zimmerman

Rizzo

Shockley

et al. 2006

Physiological Genomics

View full text Add to dashboard Cite

.-The functions of sleep and what controls it remain unanswered biological questions. According to the two-process model, a circadian process and a homeostatic process interact to regulate sleep. While progress has been made in understanding the molecular and cellular functions of the circadian process, the mechanisms of the homeostatic process remain undiscovered. We use the recently established sleep model system organism Drosophila melanogaster to examine dynamic changes in gene expression during sleep and during prolonged wakefulness in the brain. Our experimental design controls for circadian processes by killing animals at three matched time points from the beginning of the consolidated rest period [Zeitgeber time (ZT) 14)] under two conditions, sleep deprived and spontaneously sleeping. Using ANOVA at a false discovery rate of 5%, we have identified 252 genes that were differentially expressed between sleep-deprived and control groups in the Drosophila brain. Using linear trends analysis, we have separated the significant differentially expressed genes into nine temporal expression patterns relative to a common anchor point (ZT 14). The most common expression pattern is a decrease during extended wakefulness but no change during spontaneous sleep (n ϭ 114). Genes in this category were involved in protein production (n ϭ 47), calcium homeostasis, and membrane excitability (n ϭ 5). Multiple mechanisms, therefore, act to limit wakefulness. In addition, by studying the effects of the mechanical stimulus used in our deprivation studies during the period when the animals are predominantly active, we provide evidence for a previously unappreciated role for the Drosophila immune system in the brain response to stress. sleep deprivation; temporal regulation; stress SLEEP HAS BEEN OBSERVED in animal species ranging from insects to humans. We know that total sleep deprivation results in animal death (3,69,70), but the biological function of sleep remains poorly understood. With a rising prevalence of sleep restriction in our society (2, 6, 26), it becomes increasingly important to understand the function and regulation of sleep as well as the consequences of sleep deprivation on the brain.A popular conceptual framework to understand the regulation of sleep is called the two-process model. According to this model, a circadian process and a sleep-promoting (homeostatic) process, which are mechanistically distinct, interact to regulate sleep (7,8). While the cellular and molecular basis for the circadian process has been largely delineated, the homeostatic process remains poorly understood. A key feature of the homeostatic process is that the drive for sleep is proportional to the prior duration of wakefulness and that the restorative function of sleep is related to sleep time. Therefore, to understand the molecular underpinnings of the homeostatic process, wakefulness and sleep cannot be treated as single static behavioral states but, rather, as dynamic processes.To gain insight into the dynamic molecular processes th...

show abstract

Section: Discussionsupporting

confidence: 82%

Multiple mechanisms limit the duration of wakefulness in Drosophila brain

Zimmerman

Rizzo

Shockley

et al. 2006

Physiological Genomics

View full text Add to dashboard Cite

show abstract

“…We had shown previously that transcript levels of EF2 and the initiation factor 4AII, both key components of the translational machinery, are specifically increased during sleep in the brain but not in peripheral tissues, suggesting that sleep may favor brain protein synthesis ). This conclusion is in agreement with previous studies showing that leucine incorporation is higher during NREM sleep relative to waking in both rats and monkeys (Ramm and Smith, 1990;Nakanishi et al, 1997). Thus, it appears that the high levels of NA during wakefulness may inhibit brain protein synthesis, whereas the decreased release of NA during sleep may facilitate it.…”

Section: Norepinephrine and Protein Synthesissupporting

confidence: 82%

Locus Ceruleus Control of State-Dependent Gene Expression

Cirelli

Tononi²

2004

Journal of Neuroscience

View full text Add to dashboard Cite

Wakefulness and sleep are accompanied by changes in behavior and neural activity, as well as by the upregulation of different functional categories of genes. However, the mechanisms responsible for such state-dependent changes in gene expression are unknown. Here we investigate to what extent state-dependent changes in gene expression depend on the central noradrenergic (NA) system, which is active in wakefulness and reduces its firing during sleep. We measured the levels of ϳ5000 transcripts expressed in the cerebral cortex of control rats and in rats pretreated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a neurotoxin that removes the noradrenergic innervation of the cortex. We found that NA depletion reduces the expression of ϳ20% of known wakefulness-related transcripts. Most of these transcripts are involved in synaptic plasticity and in the cellular response to stress. In contrast, NA depletion increased the expression of the sleep-related gene encoding the translation elongation factor 2. These results indicate that the activity of the central NA system during wakefulness modulates neuronal transcription to favor synaptic potentiation and counteract cellular stress, whereas its inactivity during sleep may play a permissive role to enhance brain protein synthesis.

show abstract

“…Similar relationships between sleep and markers of protein synthesis have also been elucidated in numerous brain regions of the monkey (Nakanishi et al 1997). In addition, Smith et al (1991) have shown that administration of protein synthesis inhibitors during REM sleep windows in rats, thought to be critical for consolidation, prevents behavioral improvement following the sleep period, while groups that receive saline during this time show normal post-sleep learning.…”

Section: Neurochemistrymentioning

confidence: 74%

Where is the classic interference theory for sleep and memory?

Coenen

2005

Behav Brain Sci

View full text Add to dashboard Cite

Walker's target article proposes a refinement of the well known two-stage model of memory formation to explain the positive effects of sleep on consolidation. After a first stage in which a labile memory representation is formed, a further stabilisation of the memory trace takes place in the second stage, which is dependent on (REM) sleep. Walker has refined the latter stage into a stage in which a consolidation-based enhancement occurs. It is not completely clear what consolidation-based enhancement implies and how it can be dissociated from a stage for memory-stabilisation. A more serious consideration, however, is whether a second stage in memory consolidation that is solely dependent on sleep, is really necessary. The classical, passive, interference theory is able to explain adequately the findings related to the effects of sleep and memory, and can lead perhaps better to an understanding of the highly variable data in this field.

show abstract

Positive Correlations Between Cerebral Protein Synthesis Rates and Deep Sleep in Macaca mulatta

Cited by 147 publications

References 35 publications

Multiple mechanisms limit the duration of wakefulness in Drosophila brain

Multiple mechanisms limit the duration of wakefulness in Drosophila brain

Locus Ceruleus Control of State-Dependent Gene Expression

Where is the classic interference theory for sleep and memory?

Contact Info

Product

Resources

About