Chronic Mealtime Shift Disturbs Metabolic and Urinary Functions in Mice: Effects of Daily Antioxidant Supplementation.

Purpose: Through their biological clocks, organisms on this rotating planet can coordinate physiological processes according to the time of the day. However, the prevalence of circadian rhythm disorders has increased in modern society with the growing number of shift workers, elevating the risk of various diseases. In this study, we employed a mouse model to investigate the effects of urinary rhythm disturbances resulting from dietary changes commonly experienced by night shift workers.

Alternating mealtimes during pregnancy and weaning triggers behavioral changes in adult offspring.

In Brief: Mealtime changes in pregnant mice revealed impaired neurobehavioral development in mouse offspring. This study is the basis for investigating diseases associated with neurobehavioral development of adult offspring of pregnant shift-working women.

Abstract: Most organisms on Earth have a biological clock, and their physiological processes are regulated by a 1-day cycle.

Daily injection of melatonin inhibits insulin resistance induced by chronic mealtime shift.

Shift work disorders have become an emerging concern worldwide. Shift disorders encompass a wide range of illnesses that have yet to be identified. The study focused on the relationship between shift work disorders and insulin resistance.

Mealtime shift delays conception in mice.

The physiological processes of organisms in this rotating planet can adjust according to the time of day via built-in circadian clocks. However, more people are having different shift works, which can increase the risk of pathological conditions including altered reproductive function. Thus, circadian rhythm disturbance has become prevalent in the modern society.

Treadmill Exercise Alleviates Circadian Rhythm Disruption-Induced Memory Deficits by Activation of Glucocorticoid Receptor and Brain-Derived Neurotrophic Factor-Dependent Pathway.

Purpose: Circadian rhythm affects learning process, memory consolidation, and long-term memory. In this study, the alleviating effect of exercise on circadian rhythm disruption-induced memory deficits was investigated.

Methods: BMAL1 knockdown transgenic mice (BMAL1 TG) were used as the BMAL1-TG group and the BMAL1-TG with treadmill exercise group.

Astrometrically registered maps of HO and SiO masers toward VX Sagittarii.

The supergiant VX Sagittarii is a strong emitter of both HO and SiO masers. However, previous VLBI observations have been performed separately, which makes it difficult to spatially trace the outward transfer of the material consecutively. Here we present the astrometrically registered, simultaneous maps of 22.

Peroxiredoxin 6 Inhibits Osteogenic Differentiation and Bone Formation Through Human Dental Pulp Stem Cells and Induces Delayed Bone Development.

Peroxiredoxins (PRDXs) are thiol-specific antioxidant enzymes that regulate redox balance that are critical for maintaining the cellular potential for self-renewal and stemness. Stem cell-based regenerative medicine is a promising approach in tissue reconstruction. However, to obtain functional cells for use in clinical applications, stem cell technology still requires improvements.

Circadian Clock Is Involved in Regulation of Hepatobiliary Transport Mediated by Multidrug Resistance-Associated Protein 2.

There has been a growing interest in circadian regulation of the expression and function of drug transporters. In this study, we investigated circadian rhythm in the expression and function of multidrug resistance-associated protein 2 (Mrp2) in mouse liver and involvement of circadian clock in their regulations by using the circadian clock genes (period 1 and period 2) knockout mice. The mRNA and protein expression of Mrp2, P-glycoprotein, and breast cancer resistance protein was measured in the mouse liver at different times of the day.

HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism.

Metformin is a treatment of choice for patients with type 2 diabetes. Its action involves the phosphorylation of 5'-adenosine monophosphate activated protein kinase (AMPK), leading to inhibition of liver gluconeogenesis. The effects of a novel chemical compound derived from metformin, HL271, on molecular and physiological actions involving AMPK and rhythmically-expressed circadian clock genes were investigated.

A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms.

The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (Bmal1GTΔC) allele.

Aβ-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer's disease.

Background: Patients with Alzheimer's disease (AD) frequently experience disruption of their circadian rhythms, but whether and how circadian clock molecules are perturbed by AD remains unknown. AD is an age-related neurological disorder and amyloid-β (Aβ) is one of major causative molecules in the pathogenesis of AD.

Results: In this study, we investigated the role of Aβ in the regulation of clock molecules and circadian rhythm using an AD mouse model.

Do rotational shifts affect micturition patterns in real practice? A pilot study in healthy, young female nurses.

Purpose: Healthy, young individuals are known to exhibit circadian variation in urinary functions. However, the effects of chronic circadian disturbance on voiding functions are largely unknown. The present work compared the effects of rotational shifts on the micturition patterns of female nurses to that in female nurses with routine daytime shifts.

Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice.

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2::Luc knock-in mice.

Phosphorylation of LSD1 by PKCα is crucial for circadian rhythmicity and phase resetting.

The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chromatin modifiers at an organism level remains to be elucidated.

Modulation of glucocorticoid receptor induction properties by core circadian clock proteins.

Glucocorticoid (GC) plays important roles in diverse physiological processes including metabolism and immune functions. While circadian control of GC synthesis and secretion is relatively well appreciated, circadian control of GC action within target tissues remains poorly understood. Here, we demonstrate that CLOCK/BMAL1, the core circadian clock components, reduces maximal GR transactivation (A(max)) as well as efficacy (EC₅₀) by a novel mechanism that requires binding to DNA and transactivation of target genes.

Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation.

Circadian rhythm is a biological rhythm governing physiology and behavior with a period of ∼24 h. At the molecular level, circadian output is controlled by a molecular clock composed of positive and negative feedback loops in transcriptional and post-translational processes. CLOCK is a transcription factor known as a central component of the molecular clock feedback loops generating circadian oscillation.

Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm.

Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2 induction by GC signaling and its relevance to the regulation of circadian timing.

Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene.

Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5) as an interacting molecule of CRY1.

Chronic circadian disturbance by a shortened light-dark cycle increases mortality.

Chronic circadian disturbance, a condition of desynchronization between endogenous clock and environmental light-dark (LD) cycle, is known to cause adverse physiological changes including mortality. However, it is yet unclear whether these consequences result from disturbance of endogenous clock or condition of the LD cycle per se. To address this issue, we imposed 3 different periods of LD cycle (T) on wild type and functional clock-defective (Per1(-/-)Per2(-/-)) mice.

Circadian rhythms in urinary functions: possible roles of circadian clocks?

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals.

Circadian rhythms in voiding function and dysfunction.

While circadian rhythms in fluid intake, urine production, and urine storage have been substantiated in diurnal human and nocturnal rodents, the mechanism(s) underlying it is largely unknown. With the elucidations of molecular clockwork and its functional significance in mammals, new opportunities arise to investigate possible circadian control of voiding function and dysfunction, which undoubtedly needs immediate attentions of researchers in the field.

Treadmill exercise prevents aging-induced failure of memory through an increase in neurogenesis and suppression of apoptosis in rat hippocampus.

Aging leads to functional changes in the hippocampus, and consequently induces cognitive deficits, such as failure of memory. Neurogenesis in the hippocampal dentate gyrus continues throughout life, but steadily declines from early adulthood. Apoptosis occurs under various pathologic and physiologic conditions, and excessive apoptotic cell death can cause a number of functional disorders in humans.

Depression-like state in maternal rats induced by repeated separation of pups is accompanied by a decrease of cell proliferation and an increase of apoptosis in the hippocampus.

Stressful experiences, such as an unsatisfactory mother-infant relationship after delivery, can induce depressive disorders, and it is well-known that stressors impair memory function. The hippocampus plays a crucial role in memory processes. In the present study, we determined whether a depressed-like state induced by repeated separation of pups affects the memory capability of the maternal rats.