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Sleep is intimately linked to cognitive performance and exposure to traumatic stress that leads to post-traumatic stress disorder (PTSD) impairs both sleep and cognitive function. However, the contribution of pre-trauma sleep loss to subsequent trauma-dependent fear-associated memory impairment remains unstudied. We hypothesized that sleep deprivation (SD) prior to trauma exposure may increase the severity of a PTSD-like phenotype in rats exposed to single prolonged stress (SPS), a rodent model of PTSD. Rats were exposed to SPS alone, SD alone, or a combination of SPS+SD and measures of fear-associated memory impairments and vigilance state changes were compared to a group of control animals not exposed to SPS or SD. We found that SPS, and SPS+SD animals showed impaired fear-associated memory processing and that the addition of SD to SPS did not further exaggerate the effect of SPS alone. Additionally, the combination of SPS with SD results in a unique homeostatic sleep duration phenotype when compared to SD, SPS, or control animals. SPS exposure following SD represses homeostatic rebound and eliminates sleep-deprivation-induced increases in NREM sleep delta power. This work identifies a unique time frame where trauma exposure and sleep interact and identifies this window of time as a potential therapeutic treatment window for staving off the negative consequences of trauma exposure., Competing Interests: The authors have declared that no competing interests exist.

Sleep contributes to cognitive functioning and is sufficient to alter brain morphology and function. However, mechanisms underlying sleep regulation remain poorly understood. In mammals, tumor necrosis factor-alpha (TNFα) is known to regulate sleep, and cytokine expression may represent an evolutionarily ancient mechanism in sleep regulation. Here we show that the Drosophila TNFα homologue, Eiger, mediates sleep in flies. We show that knockdown of Eiger in astrocytes, but not in neurons, significantly reduces sleep duration, and total loss-of-function reduces the homeostatic response to sleep loss. In addition, we show that neuronal, but not astrocyte, expression of the TNFα receptor superfamily member, Wengen, is necessary for sleep deprivation-induced homeostatic response and for mediating increases in sleep in response to human TNFα. These data identify a novel astrocyte-to-neuron signaling mechanism in the regulation of sleep homeostasis and show that the Drosophila cytokine, Eiger, represents an evolutionarily conserved mechanism of sleep regulation across phylogeny., Competing Interests: The authors have declared that no competing interests exist.

Sleep is found widely in the animal kingdom. Despite this, few conserved molecular pathways that govern sleep across phyla have been described. The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. However, the role of FABP7 in regulating sleep remains poorly understood. We found that the missense mutation FABP7.T61M is associated with fragmented sleep in humans. This phenotype was recapitulated in mice and fruitflies bearing similar mutations: Fabp7 -deficient mice and transgenic flies that express the FABP7.T61M missense mutation in astrocytes also show fragmented sleep. These results provide novel evidence for a distinct molecular pathway linking lipid-signaling cascades within astrocytes in sleep regulation among phylogenetically disparate species.

Background: Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep)., Results: In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV). RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1-3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h) do so on average with a time constant that is similar to the time constant for the discharge of sleep need., Conclusions: We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally distinct classes of genes.

Sleep symptoms are associated with weight gain and cardiometabolic disease. The potential role of diet has been largely unexplored. Data from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) were used (n = 4552) to determine which nutrients were associated with sleep symptoms in a nationally representative sample. Survey items assessed difficulty falling asleep, sleep maintenance difficulties, non-restorative sleep and daytime sleepiness. Analyses were adjusted for energy intake, other dietary factors, exercise, body mass index (BMI) and sociodemographics. Population-weighted, logistic regression, with backwards-stepwise selection, examined which nutrients were associated with sleep symptoms. Odds ratios (ORs) reflect the difference in odds of sleep symptoms associated with a doubling in nutrient. Nutrients that were associated independently with difficulty falling asleep included (in order): alpha-carotene (OR = 0.96), selenium (OR = 0.80), dodecanoic acid (OR = 0.91), calcium (OR = 0.83) and hexadecanoic acid (OR = 1.10). Nutrients that were associated independently with sleep maintenance difficulties included: salt (OR = 1.19), butanoic acid (0.81), carbohydrate (OR = 0.71), dodecanoic acid (OR = 0.90), vitamin D (OR = 0.84), lycopene (OR = 0.98), hexanoic acid (OR = 1.25) and moisture (OR = 1.27). Nutrients that were associated independently with non-restorative sleep included butanoic acid (OR = 1.09), calcium (OR = 0.81), vitamin C (OR = 0.92), water (OR = 0.98), moisture (OR = 1.41) and cholesterol (OR = 1.10). Nutrients that were associated independently with sleepiness included: moisture (OR = 1.20), theobromine (OR = 1.04), potassium (OR = 0.70) and water (OR = 0.97). These results suggest novel associations between sleep symptoms and diet/metabolism, potentially explaining associations between sleep and cardiometabolic diseases., (© 2013 European Sleep Research Society.)

Short sleep duration is associated with weight gain and obesity, diabetes, cardiovascular disease, psychiatric illness, and performance deficits. Likewise, long sleep duration is also associated with poor physical and mental health. The role of a healthy diet in habitual sleep duration represents a largely unexplored pathway linking sleep and health. This study evaluated associations between habitual sleep parameters and dietary/nutritional variables obtained via the National Health and Nutrition Examination Survey (NHANES), 2007-2008. We hypothesized that habitual very short (<5h) short (5-6h) and long (9+h) sleep durations are associated with intake of a number of dietary nutrient variables. Overall, energy intake varied across very short (2036kcal), short (2201kcal), and long (1926kcal) sleep duration, relative to normal (2151kcal) sleep duration (p=0.001). Normal sleep duration was associated with the greatest food variety (17.8), compared to very short (14.0), short (16.5) and long (16.3) sleep duration (p<0.001). Associations between sleep duration were found across nutrient categories, with significant associations between habitual sleep duration and proteins, carbohydrates, vitamins and minerals. In stepwise analyses, significant contributors of unique variance included theobromine (long sleep RR=0.910, p<0.05), vitamin C (short sleep RR=0.890, p<0.05), tap water (short sleep RR=0.952, p<0.001; very short (<5h) sleep RR=0.941, p<0.05), lutein+zeaxanthin (short sleep RR=1.123, p<0.05), dodecanoic acid (long sleep RR=0.812, p<0.05), choline (long sleep RR=0.450, p=0.001), lycopene (very short (<5h) sleep RR=0.950, p<0.05), total carbohydrate (very short (<5h) sleep RR=0.494, p<0.05; long sleep RR=0.509, p<0.05), selenium (short sleep RR=0.670, p<0.01) and alcohol (long sleep RR=1.172, p<0.01). Overall, many nutrient variables were associated with short and/or long sleep duration, which may be explained by differences in food variety. Future studies should assess whether these associations are due to appetite dysregulation, due to short/long sleep and/or whether these nutrients have physiologic effects on sleep regulation. In addition, these data may help us better understand the complex relationship between diet and sleep and the potential role of diet in the relationship between sleep and obesity and other cardiometabolic risks., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Roh et al. report a positive feedback loop between sleep-wake irregularities and aggregation of β-amyloid peptide, suggesting that sleep alterations could be an early event in Alzheimer's disease.

Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7) on sleep and long-term memory (LTM) formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation "window" that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.

Sleep and circadian rhythms are observed broadly throughout animal phyla and influence neural plasticity and cognitive function. However, the few phylogenetically conserved cellular and molecular pathways that are implicated in these processes are largely focused on neuronal cells. Research on these topics has traditionally segregated sleep homeostatic behavior from circadian restactivity rhythms. Here we posit an alternative perspective, whereby mechanisms underlying the integration of sleep and circadian rhythms that affect behavioral state, plasticity, and cognition reside within glial cells. The brain-type fatty acid binding protein, FABP7, is part of a larger family of lipid chaperone proteins that regulate the subcellular trafficking of fatty acids for a wide range of cellular functions, including gene expression, growth, survival, inflammation, and metabolism. FABP7 is enriched in glial cells of the central nervous system and has been shown to be a clock-controlled gene implicated in sleep/wake regulation and cognitive processing. FABP7 is known to affect gene transcription, cellular outgrowth, and its subcellular localization in the fine perisynaptic astrocytic processes (PAPs) varies based on time-of-day. Future studies determining the effects of FABP7 on behavioral state- and circadian-dependent plasticity and cognitive processes, in addition to functional consequences on cellular and molecular mechanisms related to neural-glial interactions, lipid storage, and blood brain barrier integrity will be important for our knowledge of basic sleep function. Given the comorbidity of sleep disturbance with neurological disorders, these studies will also be important for our understanding of the etiology and pathophysiology of how these diseases affect or are affected by sleep. [ABSTRACT FROM AUTHOR]

Fatty acid binding proteins (FABPs) are a family of intracellular lipid chaperone proteins known to play critical roles in the regulation of fatty acid uptake and transport as well as gene expression. Brain-type fatty acid binding protein (FABP7) is enriched in astrocytes and has been implicated in sleep/wake regulation and neurodegenerative diseases; however, the precise mechanisms underlying the role of FABP7 in these biological processes remain unclear. FABP7 binds to both arachidonic acid (AA) and docosahexaenoic acid (DHA), resulting in discrete physiological responses. Here, we propose a dichotomous role for FABP7 in which ligand type determines the subcellular translocation of fatty acids, either promoting wakefulness aligned with Alzheimer’s pathogenesis or promoting sleep with concomitant activation of anti-inflammatory pathways and neuroprotection. We hypothesize that FABP7-mediated translocation of AA to the endoplasmic reticulum of astrocytes increases astrogliosis, impedes glutamatergic uptake, and enhances wakefulness and inflammatory pathways via COX- 2 dependent generation of pro-inflammatory prostaglandins. Conversely, we propose that FABP7-mediated translocation of DHA to the nucleus stabilizes astrocyte-neuron lactate shuttle dynamics, preserves glutamatergic uptake, and promotes sleep by activating anti-inflammatory pathways through the peroxisome proliferator-activated receptor-g transcriptional cascade. Importantly, this model generates several testable hypotheses applicable to other neurodegenerative diseases, including amyotrophic lateral sclerosis and Parkinson’s disease. [ABSTRACT FROM AUTHOR]

The article taillights research papers on the influence of sleep and circadian rhythms on brain plasticity-related processes. The topics covered include the importance of using invertebrate model systems for examining relationships between sleep, clocks and memory, evidence for nitric oxide in the diurnal regulation of olfactory memory in the hawkmoth, Manduca sexta, and sleep-and wake-associated changes in CA1 hippocampal network activity during memory consolidation.