Circadian and Age-Related Variations of Amino Acids Levels in Brains: Correlations and Descriptive Dimensions.

A comprehensive view of whole-brain amino acid levels holds the potential to provide valuable insights into the brain's state, given the mutual interconnections through metabolism, food intake, and neurotransmission. We tested this concept by evaluating free amino acid levels in single brains across 24 h and at two different ages. A large proportion of these amino acids displayed time-of-day variations, and a subset exhibited age-dependent variations.

Decoding the nexus: branched-chain amino acids and their connection with sleep, circadian rhythms, and cardiometabolic health.

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and, either directly or indirectly, overall body health, encompassing metabolic and cardiovascular well-being. Given the heightened metabolic activity of the brain, there exists a considerable demand for nutrients in comparison to other organs. Among these, the branched-chain amino acids, comprising leucine, isoleucine, and valine, display distinctive significance, from their contribution to protein structure to their involvement in overall metabolism, especially in cerebral processes.

Salivary α-amylase as a marker of sleep disorders: A theoretical review.

Sleep disorders are commonplace in our modern societies. Specialized hospital departments are generally overloaded, and sleep assessment is an expensive process in terms of equipment, human resources, and time. Biomarkers would usefully complement current measures in the screening and follow-up of sleep disorders and their daytime repercussions.

Pallidin function in Drosophila surface glia regulates sleep and is dependent on amino acid availability.

The Pallidin protein is a central subunit of a multimeric complex called biogenesis of lysosome-related organelles complex 1 (BLOC1) that regulates specific endosomal functions and has been linked to schizophrenia. We show here that downregulation of Pallidin and other members of BLOC1 in the surface glia, the Drosophila equivalent of the blood-brain barrier, reduces and delays nighttime sleep in a circadian-clock-dependent manner. In agreement with BLOC1 involvement in amino acid transport, downregulation of the large neutral amino acid transporter 1 (LAT1)-like transporters JhI-21 and mnd, as well as of TOR (target of rapamycin) amino acid signaling, phenocopy Pallidin knockdown.

Interest of the BLAST paradigm and salivary markers for the evaluation of sleepiness in drivers.

Objectives: Sleepiness is associated with decreased cognitive abilities and remains one of the main causes of fatal road accidents. The tools currently available to assess sleepiness, such as questionnaires, are subject to intra- and inter-individual variability, while multiple sleep latency tests are only feasible in few sleep laboratories. The main objective of this study was to explore new potential markers (neurocognitive, biological) to objectively assess sleepiness in drivers.

Intellectual Abilities of Children with Narcolepsy.

High cognitive functioning could be a protective factor for school difficulties, behavioral and mood impairments in children with narcolepsy. To investigate this factor, we studied the intellectual abilities of 74 children with narcolepsy (43 boys, 11.7 years old at diagnosis, 91% of cataplexies, 64% obese, 100% HLA positive for DR-DQB1*06:02).

Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity.

Glial cells are early sensors of neuronal injury and can store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the functions of the RNA-binding protein, SPEN/SHARP, in the context of Parkinson's disease (PD). Using a data-mining approach, we found that SPEN/SHARP is one of many astrocyte-expressed genes that are significantly differentially expressed in the substantia nigra of PD patients compared with control subjects.

LAT1-like transporters regulate dopaminergic transmission and sleep in Drosophila.

Amino acid transporters are involved in functions reportedly linked to the sleep/wake cycle: neurotransmitter synthesis and recycling, the regulation of synaptic strength, protein synthesis, and energy metabolism. In addition, the existence of bidirectional relationships among extracellular content, transport systems, and sleep/wake states is receiving emerging support. Nevertheless, the connection between amino acid transport and sleep/wake regulation remains elusive.

Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss.

Although patients with primary insomnia experience sleep disruption, they are able to maintain normal performance on a variety of cognitive tasks. This observation suggests that insomnia may be a condition where predisposing factors simultaneously increase the risk for insomnia and also mitigate against the deleterious consequences of waking. To gain insight into processes that might regulate sleep and buffer neuronal circuits during sleep loss, we manipulated three genes, (, () and the GABA receptor (), that were differentially modulated in a model of insomnia.

Amyloid Precursor Protein in Glia Regulates Sleep and Genes Involved in Glutamate Recycling.

Amyloid precursor protein (App) plays a crucial role in Alzheimer's disease via the production and deposition of toxic β-amyloid peptides. App is heavily expressed in neurons, the focus of the vast majority of studies investigating its function. Meanwhile, almost nothing is known about App's function in glia, where it is also expressed, and can potentially participate in the regulation of neuronal physiology.

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration.

Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption.

Individuals frequently find themselves confronted with a variety of challenges that threaten their wellbeing. While some individuals face these challenges efficiently and thrive (resilient) others are unable to cope and may suffer persistent consequences (vulnerable). Resilience/vulnerability to sleep disruption may contribute to the vulnerability of individuals exposed to challenging conditions.

Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila.

Background And Study Objectives: Flies mutant for the canonical clock protein cycle (cyc(01)) exhibit a sleep rebound that is ∼10 times larger than wild-type flies and die after only 10 h of sleep deprivation. Surprisingly, when starved, cyc(01) mutants can remain awake for 28 h without demonstrating negative outcomes. Thus, we hypothesized that identifying transcripts that are differentially regulated between waking induced by sleep deprivation and waking induced by starvation would identify genes that underlie the deleterious effects of sleep deprivation and/or protect flies from the negative consequences of waking.

Circadian modulation of consolidated memory retrieval following sleep deprivation in Drosophila.

Objectives: Several lines of evidence indicate that sleep plays a critical role in learning and memory. The aim of this study was to evaluate anesthesia resistant memory following sleep deprivation in Drosophila.

Design: Four to 16 h after aversive olfactory training, flies were sleep deprived for 4 h.

Effects of GF-015535-00, a novel α1 GABA A receptor ligand, on the sleep-wake cycle in mice, with reference to zolpidem.

Study Objectives: Novel, safe, and efficient hypnotic compounds capable of enhancing physiological sleep are still in great demand in the therapy of insomnia. This study compares the sleep-wake effects of a new α1 GABA(A) receptor subunit ligand, GF-015535-00, with those of zolpidem, the widely utilized hypnotic compound.

Methods: Nine C57Bl6/J male mice were chronically implanted with electrodes for EEG and sleep-wake monitoring.

Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila.

The role of the transmembrane receptor Notch in the adult brain is poorly understood. Here, we provide evidence that bunched, a negative regulator of Notch, is involved in sleep homeostasis. Genetic evidence indicates that interfering with bunched activity in the mushroom bodies (MBs) abolishes sleep homeostasis.

Sleep deprivation during early-adult development results in long-lasting learning deficits in adult Drosophila.

Study Objectives: Multiple lines of evidence indicate that sleep is important for the developing brain, although little is known about which cellular and molecular pathways are affected. Thus, the aim of this study was to determine whether the early adult life of Drosophila, which is associated with high amounts of sleep and critical periods of brain plasticity, could be used as a model to identify developmental processes that require sleep.

Subjects: Wild type Canton-S Drosophila melanogaster.

Behavioral consequences of dopamine deficiency in the Drosophila central nervous system.

The neuromodulatory function of dopamine (DA) is an inherent feature of nervous systems of all animals. To learn more about the function of neural DA in Drosophila, we generated mutant flies that lack tyrosine hydroxylase, and thus DA biosynthesis, selectively in the nervous system. We found that DA is absent or below detection limits in the adult brain of these flies.

The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss.

Extended periods of waking result in physiological impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Sleep homeostasis, as with other behaviors, is influenced by both genes and environment.

Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.

Study Objectives: Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain.

Identifying sleep regulatory genes using a Drosophila model of insomnia.

Although it is widely accepted that sleep must serve an essential biological function, little is known about molecules that underlie sleep regulation. Given that insomnia is a common sleep disorder that disrupts the ability to initiate and maintain restorative sleep, a better understanding of its molecular underpinning may provide crucial insights into sleep regulatory processes. Thus, we created a line of flies using laboratory selection that share traits with human insomnia.

D1 receptor activation in the mushroom bodies rescues sleep-loss-induced learning impairments in Drosophila.

Background: Extended wakefulness disrupts acquisition of short-term memories in mammals. However, the underlying molecular mechanisms triggered by extended waking and restored by sleep are unknown. Moreover, the neuronal circuits that depend on sleep for optimal learning remain unidentified.