Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep

Methippara, Melvi; Bashir, Tariq; Kumar, Sunil; Alam, Noor; Szymusiak, Ronald; McGinty, Dennis

doi:10.1152/ajpregu.90765.2008

Cited by 22 publications

(20 citation statements)

References 47 publications

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“…Phosphoe-IF2α levels were significantly reduced in the PBA treated aged flies subjected to sleep deprivation. Changes in p-eIF2α can be directly linked to the behavioral changes in the aged flies given that increased p-eIF2α facilitates baseline (Methippara et al 2009) and recovery sleep (Methippara et al 2012). The reduced eIF2α phosphorylation in PBA treated animals may account for the improved homeostatic response in the aged SD flies.…”

Section: Discussionmentioning

confidence: 99%

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis

Brown

Chan

Zimmerman

et al. 2014

Neurobiology of Aging

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Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge.

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Section: Discussionmentioning

confidence: 99%

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis

Brown

Chan

Zimmerman

et al. 2014

Neurobiology of Aging

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“…One of the ways the cell relieves ER stress is to decrease protein translation(48) through phosphorylation of elF2α by phosphorylated pancreatic ER kinase (P-PERK). It has been hypothesized that P-elF2α is a signal for sleep(49). Thus it is plausible that the increased fat intake through reduced lipid synthesis delays the phosphorylation of elF2a and hence the signal for sleep.…”

Section: Discussionmentioning

confidence: 99%

Relationships among dietary nutrients and subjective sleep, objective sleep, and napping in women

et al. 2010

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Objective-To describe which dietary nutrient variables are related to subjective and objective habitual sleep and subjective and objective napping.Methods-Participants were 459 postmenopausal women enrolled in the Women's Health Initiative. Objective sleep was estimated using one week of actigraphy. Subjective sleep was prospectively estimated with a daily sleep diary. Dietary nutrients were calculated from food frequency questionnaires.Results-The most significant correlations were with subjective napping, including (from strongest to weakest): total fat,

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“…Recent data suggest that extending wakefulness leads to ER stress and several different strategies, including the use of specific pharmacological agents that modify the process [85], support this concept. Whether sleep deprivation leads to ER stress in the brain in humans is unknown currently, although it seems likely that this will be the case because this has been demonstrated in all species studied to date.…”

Section: Discussionmentioning

confidence: 99%

What are microarrays teaching us about sleep?

Mackiewicz

Zimmerman

Shockley

et al. 2009

Trends in Molecular Medicine

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Many fundamental questions about sleep remain unanswered. The presence of sleep across phyla suggests that it must serve a basic cellular and/or molecular function. Microarray studies, performed in several model systems, have identified classes of genes that are sleep-state regulated. This has led to the following concepts: first, a function of sleep is to maintain synaptic homeostasis; second, sleep is a stage of macromolecule biosynthesis; third, extending wakefulness leads to downregulation of several important metabolic pathways; and, fourth, extending wakefulness leads to endoplasmic reticulum stress. In human studies, microarrays are being applied to the identification of biomarkers for sleepiness and for the common debilitating condition of obstructive sleep apnea. High-throughput approaches to study gene expressionThe search for genes involved in regulation by, and of, sleep and wakefulness and the quest to understand the functions of sleep at the molecular level began a decade before the advent of microarrays. Several candidate genes were studied to elucidate their roles in sleep and wakefulness (for a review, see [1]). Subtractive hybridization carried out on brain mRNA from sleep-deprived rats, performed in the early 1990s, was the first 'high-throughput' attempt to identify such genes [2]. Later, the application of differential display [3] broadened the candidate gene and subtractive hybridization approaches to screen for genes whose functions were poorly characterized or previously unknown.As a result of sequencing efforts, there has been an exponential growth in the amount of information available about the DNA sequence of the human genome (e.g., see [4]) as well as the genomes of various model organisms (e.g., see [5,6]). Consequently, thousands of genes have been discovered, including many novel genes for which sequences were unavailable previously. The role of many of these genes is unknown. This facilitated the advent of microarray approaches.A microarray contains tens of thousands of genes and is a tool for simultaneous measurement of their expression. Significant advances in gene annotations, progress in development and © 2008 Elsevier Ltd. All rights reserved.Corresponding author: Pack, A.I. (pack@mail.med.upenn.edu). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Microarrays in sleep researchMicroarrays offer a new window on the difference between the sleeping and awake brain and hold the promise of facilitating answers to some of the major questions in sleep biology (Box 1; see also [9][10][11]).These questions are releva...

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Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep

Cited by 22 publications

References 47 publications

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis

Relationships among dietary nutrients and subjective sleep, objective sleep, and napping in women

What are microarrays teaching us about sleep?

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