Coordinating the energetic strategy of glia and neurons for memory.

Memory consolidation requires rapid energy supply to neurons. In a recent study, Francés et al. revealed the signal by which a neuron commands glia to limit fatty acid synthesis in favor of metabolite export during memory formation in Drosophila melanogaster.

A carnitine transporter at the blood-brain barrier modulates sleep via glial lipid metabolism in .

To regulate brain function, peripheral compounds must traverse the blood-brain barrier (BBB), an interface between the brain and the circulatory system. To determine whether specific transport mechanisms are relevant for sleep, we conducted a BBB-specific inducible RNAi knockdown (iKD) screen for genes affecting sleep in . We observed reduced sleep with knockdown of solute carrier , a carnitine transporter, as determined by isotope flux.

Glia: The Cellular Glue that binds Circadian Rhythms and Sleep.

Glia are increasingly appreciated as serving an important function in the control of sleep and circadian rhythms. Glial cells in Drosophila and mammals regulate daily rhythms of locomotor activity and sleep as well as homeostatic rebound following sleep deprivation. In addition, they contribute to proposed functions of sleep, with different functions mapping to varied glial subtypes.

Modulation of RNA processing genes during sleep-dependent memory.

Memory consolidation in can be sleep-dependent or sleep-independent, depending on the availability of food. The anterior posterior (ap) alpha'/beta' (α'/β') neurons of the mushroom body (MB) are required for sleep-dependent memory consolidation in flies fed after training. These neurons are also involved in the increase of sleep after training, suggesting a coupling of sleep and memory.

Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms.

Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent changes in peripheral rhythms, we compared the ability of human serum from young and old individuals to synchronize circadian rhythms in culture. We collected blood from apparently healthy young (age 25-30) and old (age 70-76) individuals at 14:00 and used the serum to synchronize cultured fibroblasts.

A hypothalamic circuit mechanism underlying the impact of stress on memory and sleep.

Stress profoundly affects sleep and memory processes. Stress impairs memory consolidation, and similarly, disruptions in sleep compromise memory functions. Yet, the neural circuits underlying stress-induced sleep and memory disturbances are still not fully understood.

An integrative analysis of cell-specific transcriptomics and nuclear proteomics of sleep-deprived mouse cerebral cortex.

Sleep regulation follows a homeostatic pattern. The mammalian cerebral cortex is the repository of homeostatic sleep drive and neurons and astrocytes of the cortex are principal responders of sleep need. The molecular mechanisms by which these two cell types respond to sleep loss are not yet clearly understood.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation.

Quiescence Enhances Survival during Viral Infection in .

Infection causes reduced activity, anorexia, and sleep, which are components of the phylogenetically conserved but poorly understood sickness behavior. We developed a model to study quiescence during chronic infection, using infection with the Orsay virus. The Orsay virus infects intestinal cells yet strongly affects behavior, indicating gut-to-nervous system communication.

Do metabolic deficits contribute to sleep disruption in monogenic intellectual disability syndromes?

Intellectual disability is defined as limitations in cognitive and adaptive behavior that often arise during development. Disordered sleep is common in intellectual disability and, given the importance of sleep for cognitive function, it may contribute to other behavioral phenotypes. Animal models of intellectual disability, in particular of monogenic intellectual disability syndromes (MIDS), recapitulate many disease phenotypes and have been invaluable for linking some of these phenotypes to specific molecular pathways.

Energetic demands regulate sleep-wake rhythm circuit development.

Sleep and feeding patterns lack strong daily rhythms during early life. As diurnal animals mature, feeding is consolidated to the day and sleep to the night. In , circadian sleep patterns are initiated with formation of a circuit connecting the central clock to arousal output neurons; emergence of circadian sleep also enables long-term memory (LTM).

Hypermetabolic state is associated with circadian rhythm disruption in mouse and human cancer cells.

Crosstalk between metabolism and circadian rhythms is a fundamental building block of multicellular life, and disruption of this reciprocal communication could be relevant to disease. Here, we investigated whether maintenance of circadian rhythms depends on specific metabolic pathways, particularly in the context of cancer. We found that in adult mouse fibroblasts, ATP levels were a major contributor to signal from a clock gene luciferase reporter, although not necessarily to the strength of circadian cycling.

Senescent glia link mitochondrial dysfunction and lipid accumulation.

Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumour formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear.

Altered Metabolism during the Dark Period in Drosophila Short Sleep Mutants.

Sleep is regulated via circadian mechanisms, but effects of sleep disruption on physiological rhythms, in particular metabolic cycling, remain unclear. To examine this question, we probed diurnal metabolic alterations of two short sleep mutants, and Samples were collected with high temporal sampling (every 2 h) over 24 h under a 12:12 light:dark cycle, and profiling was done using an ion-switching LCMS/MS method. Fewer metabolites with 24 h oscillations were noted with short sleep (50 and 46 in and , BH.

Norepinephrine Drives Sleep Fragmentation Activation of Asparagine Endopeptidase, Locus Ceruleus Degeneration, and Hippocampal Amyloid-β Accumulation.

Chronic sleep disruption (CSD), from insufficient or fragmented sleep and is an important risk factor for Alzheimer's disease (AD). Underlying mechanisms are not understood. CSD in mice results in degeneration of locus ceruleus neurons (LCn) and CA1 hippocampal neurons and increases hippocampal amyloid-β (Aβ), entorhinal cortex (EC) tau phosphorylation (p-tau), and glial reactivity.

Using routinely collected clinical data for circadian medicine: A review of opportunities and challenges.

A wealth of data is available from electronic health records (EHR) that are collected as part of routine clinical care in hospitals worldwide. These rich, longitudinal data offer an attractive object of study for the field of circadian medicine, which aims to translate knowledge of circadian rhythms to improve patient health. This narrative review aims to discuss opportunities for EHR in studies of circadian medicine, highlight the methodological challenges, and provide recommendations for using these data to advance the field.

Infralimbic activity during REM sleep facilitates fear extinction memory.

Rapid eye movement (REM) sleep is known to facilitate fear extinction and play a protective role against fearful memories. Consequently, disruption of REM sleep after a traumatic event may increase the risk for developing PTSD. However, the underlying mechanisms by which REM sleep promotes extinction of aversive memories remain largely unknown.