Search

Introduction: The relationships between the feeding rhythm, sleep and cognition in Alzheimer's disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions. Methods: The 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-h light phase (light-fed groups) or the 12-h dark phase (dark-fed groups). Sleep (electroencephalographic/ electromyographic) recording and cognitive behavior measures were collected. Results: The 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxiety-associated behavior. These emotional and cognitive measures are correlated with REM amount. Discussion: Our study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males. [ABSTRACT FROM AUTHOR]

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbially modified metabolites over time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides (GOS) and polydextrose (PDX)), compared to a control diet, would consistently impact the gut microbiome and microbially modified bile acids over time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiomes and metabolomes were examined using 16S rRNA gene sequencing and untargeted LC–MS/MS analysis. Dietary prebiotics altered the beta diversity, relative abundance of bacterial genera, and microbially modified bile acids over time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by the prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbially modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites, supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem. [ABSTRACT FROM AUTHOR]

His favorite version, glasses of the finest single malt Scotch!" Johnson: What Fred and Gene and Russ were saying reminded me of my favorite Pitt story, which has to do with what happened to Pitt during World War II. So, for example, Pitt said that one time Arthur Kornberg (the Nobel Laureate, 1959) heard Pitt give a lecture and afterward Kornberg said, "Pitt, the reason I got the Nobel Prize is because I focused on this one enzyme and I just learned everything about this single enzyme. Terry Page had become a postdoc in Pitt's laboratory slightly in advance of my arrival in the Kennedy lab, and Pitt and Don thought the two of us might be able to be the start of a collaboration between the two labs. Along with Erwin Bünning and Jürgen Aschoff, Colin Stephenson Pittendrigh (aka "Pitt") (Figure 1) is considered to be a founder of the modern field of chronobiology. Johnson: Just adding to your point, Bill; one of the things that was very magnanimous about Pitt was that he adjusted his response to people based on who they were and that, for example, if a graduate student asked a question in a lecture and it was a stupid question, Pitt would be very supportive. [Extracted from the article]

Continuous disruption of circadian rhythms, as seen in human shift workers, has been associated with the development of a number of adverse mental and physiological conditions. However, scientific evidence linking circadian disruption to overall health, particularly in animal models, is not well documented. In this study, we have demonstrated that exposing C57BL/6J mice to 12-h phase shifts every 5 days for 3 mo had no effect on body weight or intestinal physiology. However, when animals were further challenged with dextran sodium sulfate to induce colitis, chronic shifting of the light-dark cycle led to a dramatic increase in the progression of the colitis as indicated by reduced body weight, abnormal intestinal histopathology, and an exacerbated inflammatory response. These data indicate that circadian disruption is an important predisposing factor that may provoke the onset or worsening of various disease states such as inflammatory disorders. This study provides further evidence for continued investigations using animal models of circadian disruption to examine the consequences of circadian disruption on health when organisms are faced with a 'challenging' environment. circadian rhythms; shift work; circadian disorganization

Recent epidemiological, clinical, and experimental studies have demonstrated important links between sleep duration and architecture, circadian rhythms, and metabolism, although the genetic pathways that interconnect these processes are not well understood. Leptin is a circulating hormone and major adiposity signal involved in long-term energy homeostasis. In this study, we tested the hypothesis that leptin deficiency leads to impairments in sleep-wake regulation. Male ob/ob mice, a genetic model of leptin deficiency, had significantly disrupted sleep architecture with an elevated number of arousals from sleep [wild-type (WT) mice, 108.2 [+ or -] 7.2 vs. ob/ob mice, 148.4 [+ or -]4.5, P < 0.001] and increased stage shifts (WT, 519.1 [+ or -] 25.2 vs. ob/ob, 748.0 [+ or -] 38.8, P < 0.001) compared with WT mice. Ob/ob mice also had more frequent, but shorter-lasting sleep bouts compared with WT mice, indicating impaired sleep consolidation. Interestingly, ob/ob mice showed changes in sleep time, with increased amounts of 24-h non-rapid eye movement (NREM) sleep (WT, 601.5 [+ or -] 10.8 vs. ob/ob, 669.2 [+ or -] 13.4 min, P < 0.001). Ob/ob mice had overall lower body temperature (WT, 35.1 [+ or -] 0.2 vs. ob/ob, 33.4 [+ or -] 0.2[degrees]C, P < 0.001) and locomotor activity counts (WT, 25125 [+ or -] 2137 vs. ob/ob, 5219 [+ or -] 1759, P < 0.001). Ob/ob mice displayed an attenuated diurnal rhythm of sleep-wake stages, NREM delta power, and locomotor activity. Following sleep deprivation, ob/ob mice had smaller amounts of NREM and REM recovery sleep, both in terms of the magnitude and the duration of the recovery response. In combination, these results indicate that leptin deficiency disrupts the regulation of sleep architecture and diurnal rhythmicity. obesity; sleep time; locomotor activity; sleep fragmentation; circadian rhythms; energy metabolism

Sleep disruption is a challenging and exceedingly common physiological state that contributes to a wide range of biochemical and molecular perturbations and has been linked to numerous adverse health outcomes. Modern society exerts significant pressure on the sleep/wake cycle via myriad factors, including exposure to electric light, psychological stressors, technological interconnection, jet travel, shift work, and widespread use of sleep-affecting compounds. Interestingly, recent research has identified a link between the microbiome and the regulation of sleep, suggesting that interventions targeting the microbiome may offer unique therapeutic approaches to challenges posed by sleep disruption. In this study, we test the hypothesis that administration of a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) in adult male rats improves sleep in response to repeated sleep disruption and during recovery sleep. We found that animals fed the GOS/PDX prebiotic diet for 4 weeks exhibit increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during 5 days of sleep disruption and increased total sleep time during 24 h of recovery from sleep disruption compared to animals fed a control diet, despite similar baseline sleep characteristics. Further, the GOS/PDX prebiotic diet led to significant changes in the fecal microbiome. Consistent with previous reports, the prebiotic diet increased the relative abundance of the species Parabacteroides distasonis , which positively correlated with sleep parameters during recovery sleep. Taken together, these findings suggest that the GOS/PDX prebiotic diet may offer an approach to improve resilience to the physiologic challenge of sleep disruption, in part through impacts on the microbiome. [ABSTRACT FROM AUTHOR]

Affective behaviours and mental health are profoundly affected by disturbances in circadian rhythms. Casein kinase 1 epsilon (CSNK1E) is a core component of the circadian clock. Mice with tau or null mutation of this gene have shortened and lengthened circadian period respectively. Here, we examined anxiety‐like, fear, and despair behaviours in both male and female mice of these two different mutants. Compared with wild‐type mice, we found reductions in fear and anxiety‐like behaviours in both mutant lines and in both sexes, with the tau mutants exhibiting the greatest phenotypic changes. However, the behavioural despair had distinct phenotypic patterns, with markedly less behavioural despair in female null mutants, but not in tau mutants of either sex. To determine whether abnormal light entrainment of tau mutants to 24‐h light–dark cycles contributes to these phenotypic differences, we also examined these behaviours in tau mutants on a 20‐h light–dark cycle close to their endogenous circadian period. The normalized entrainment restored more wild‐type‐like behaviours for fear and anxiety, but it induced behavioural despair in tau mutant females. These data show that both mutations of Csnk1e broadly affect fear and anxiety‐like behaviours, while the effects on behavioural despair vary with genetics, photoperiod, and sex, suggesting that the mechanisms by which Csnk1e affects fear and anxiety‐like behaviours may be similar, but distinct from those affecting behavioural despair. Our study also provides experimental evidence in support of the hypothesis of beneficial outcomes from properly entrained circadian rhythms in terms of the anxiety‐like and fear behaviours. [ABSTRACT FROM AUTHOR]