Social stress alters sleep in FGF21-deficient mice.

Although several previous studies have suggested a relationship between sleep and the stress response, the mechanism underlying this relationship remains largely unknown. Here, we show that fibroblast growth factor 21 (FGF21), a lipid metabolism-related hormone, may play a role in this relationship. In this study, we examined differences in the stress response between FGF21 knockout (KO) mice and wild-type (WT) mice after social defeat stress (SDS).

Dual orexin receptor antagonist drug suvorexant can help in amelioration of predictable chronic mild stress-induced hyperalgesia.

Aims: This study aimed to evaluate the involvement of the orexin system in predictable chronic mild stress (PCMS) and the effects of suvorexant, a dual orexin receptor antagonist, on nociceptive behavior in PCMS.

Materials And Methods: Male C57BL/6 J mice were separated into various PCMS groups: a control group with sawdust on the floor of the rearing cage (C), a group with mesh wire on the floor (M), and a group with water just below the mesh wire (W). Activation of lateral hypothalamic orexin neurons was assessed using immunofluorescence.

Feeding Rhythm-Induced Hypothalamic Agouti-Related Protein Elevation via Glucocorticoids Leads to Insulin Resistance in Skeletal Muscle.

Circadian phase shifts in peripheral clocks induced by changes in feeding rhythm often result in insulin resistance. However, whether the hypothalamic control system for energy metabolism is involved in the feeding rhythm-related development of insulin resistance is unknown. Here, we show the physiological significance and mechanism of the involvement of the agouti-related protein (AgRP) in evening feeding-associated alterations in insulin sensitivity.

Pain sensitivity increases with sleep disturbance under predictable chronic mild stress in mice.

Even though it has been well documented that stress can lead to the development of sleep disorders and the intensification of pain, their relationships have not been fully understood. The present study was aimed at investigating the effects of predictable chronic mild stress (PCMS) on sleep-wake states and pain threshold, using the PCMS rearing conditions of mesh wire (MW) and water (W) for 21 days. Exposure to PCMS decreased the amount of non-rapid eye movement (NREM) sleep during the dark phase.

Intracranial mast cells contribute to the control of social behavior in male mice.

Mast cells (MCs) exist intracranially and have been reported to affect higher brain functions in rodents. However, the role of MCs in the regulation of emotionality and social behavior is unclear. In the present study, using male mice, we examined the relationship between MCs and social behavior and investigated the underlying mechanisms.

Sleep profile during fasting in PPAR-alpha knockout mice.

Peroxisome proliferator-activated receptor alpha (PPARα) is a transcription factor that belongs to the nuclear receptor family and plays an important role in regulating gene expression associated with lipid metabolism. PPARα promotes hepatic fatty acid oxidation and ketogenesis in response to fasting. Because energy metabolism is known to affect sleep regulation, manipulations that change PPARα are likely to affect sleep and other physiological phenotypes.

Rotigotine suppresses sleep-related muscle activity augmented by injection of dialysis patients' sera in a mouse model of restless legs syndrome.

Idiopathic restless legs syndrome (RLS) has a genetic basis wherein BTBD9 is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of BTBD9 and end-stage renal disease to RLS pathophysiology.

Dopamine stimulation of the septum enhances exercise efficiency during complicated treadmill running in mice.

We aimed to identify the neurotransmitters and brain regions involved in exercise efficiency in mice during continuous complicated exercises. Male C57BL/6J mice practiced treadmill running with intermittent obstacles on a treadmill for 8 days. Oxygen uptake (VO) during treadmill running was measured as exercise efficiency.

Role of orexin in exercise-induced leptin sensitivity in the mediobasal hypothalamus of mice.

Orexin is known as an important neuropeptide in the regulation of energy metabolism. However, the role of orexin in exercise-induced leptin sensitivity in the hypothalamus has been unclear. In this study, we determined the effect of transient treadmill exercise on leptin sensitivity in the mediobasal hypothalamus (MBH) of mice and examined the role of orexin in post-exercise leptin sensitivity.

Sufficient intake of high-fat food attenuates stress-induced social avoidance behavior.

Aims: Psychosocial stress is a form of mental stress associated with human relationships that underlies the pathogenesis of mental disorders such as depression. Previous studies have suggested that intake of energy-dense foods, also known as "palatable foods," can relieve psychosocial stress. However, it remains unclear whether the volume of palatable food affects abnormal behavior induced by psychosocial stress.

Enhancement of fear learning in PPARα knockout mice.

Peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily and regulates fatty acid oxidation. Although PPARα is expressed not only in the peripheral tissues but also in the brain, its role in higher brain function is unclear. In this study, we investigated the role of PPARα in the control of behavior, including memory/learning and mood change, using PPARα knockout (KO) mice.

Mast cell involvement in glucose tolerance impairment caused by chronic mild stress with sleep disturbance.

We have developed a chronic mild stress (MS) mouse model by simply rearing mice on a wire net for 3 weeks and investigated the effects of MS on glucose homeostasis and sleep. MS mice showed impaired glucose tolerance and disturbed sleep. One-week treatment with a histamine H1 receptor antagonist (H1RA) ameliorated the glucose intolerance and improved sleep quality in MS mice.

Wake-promoting effects of ONO-4127Na, a prostaglandin DP1 receptor antagonist, in hypocretin/orexin deficient narcoleptic mice.

Prostaglandin (PG)D2 is an endogenous sleep substance, and a series of animal studies reported that PGD2 or PGD2 receptor (DP1) agonists promote sleep, while DP1 antagonists promote wakefulness. This suggests the possibility of use of PG DP1 antagonists as wake-promoting compounds. We therefore evaluated the wake-promoting effects of ONO-4127Na, a DP1 antagonist, in a mouse model of narcolepsy (i.

Late feeding in the active period decreases slow-wave activity.

Aims: Sleep and feeding behaviors closely interact to maintain energy homeostasis. While it is known that sleep disorders can lead to various metabolic issues such as insulin resistance, the mechanism for this effect is poorly understood. We thus investigated whether different feeding rhythms during the active period affect sleep-wake regulation.

Sleep as a biological problem: an overview of frontiers in sleep research.

Sleep is a physiological process not only for the rest of the body but also for several brain functions such as mood, memory, and consciousness. Nevertheless, the nature and functions of sleep remain largely unknown due to its extremely complicated nature and lack of optimized technology for the experiments. Here we review the recent progress in the biology of the mammalian sleep, which covers a wide range of research areas: the basic knowledge about sleep, the physiology of cerebral cortex in sleeping animals, the detailed morphological features of thalamocortical networks, the mechanisms underlying fluctuating activity of autonomic nervous systems during rapid eye movement sleep, the cutting-edge technology of tissue clearing for visualization of the whole brain, the ketogenesis-mediated homeostatic regulation of sleep, and the forward genetic approach for identification of novel genes involved in sleep.

Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model.

Ketone body metabolism and sleep homeostasis in mice.

A link has been established between energy metabolism and sleep homeostasis. The ketone bodies acetoacetate and β-hydroxybutyrate, generated from the breakdown of fatty acids, are major metabolic fuels for the brain under conditions of low glucose availability. Ketogenesis is modulated by the activity of peroxisome proliferator-activated receptor alpha (PPARα), and treatment with a PPAR activator has been shown to induce a marked increase in plasma acetoacetate and decreased β-hydroxybutyrate in mice, accompanied by increased slow-wave activity during non-rapid eye movement (NREM) sleep.

Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors.

Maternal dietary restriction alters offspring's sleep homeostasis.

Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD) or 50% dietary restriction (DR) groups from gestation day 12 to parturition.

The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice.

The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation of memory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as a key molecule in RA-mediated anti-AD mechanisms.

[Sleep regulatory mechanisms].

The fact that resting wakefulness does not satisfy the need for sleep suggests that sleep has a critical role for the brain, probably for its maintenance or repair. Neuronal oxidative stress, neuroinflammation, or energy insufficiency in the brain is now considered to be a trigger or cause for sleep induction. And the timing for sleep is controlled by circadian clock which also exists in the brain.

The role of ATP in sleep regulation.

One of the functions of sleep is to maintain energy balance in the brain. There are a variety of hypotheses related to how metabolic pathways interact with sleep/wake regulation. A major finding that demonstrates an interaction between sleep and metabolic homeostasis is the involvement of adenosine in sleep homeostasis.

Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome.

Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Ca(v)1.2 that is associated with developmental delay and autism.

Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice.

Vitamin A is a common lipophilic vitamin, and its function is mainly mediated by the binding of its metabolite retinoic acid to retinoic acid receptors (RARs) and retinoid X receptors. Recently, it was reported that the expression of the RARb (an RAR subtype) gene determines the contribution of the delta oscillation in the sleep electroencephalogram (EEG) patterns in mice. We also reported that 4-week dietary deficiency of vitamin A (VAD) causes the attenuation of delta power in sleep and spontaneous activity in mice.

Refeeding after a 24-hour fasting deepens NREM sleep in a time-dependent manner.

Sleep/wake cycle is regulated by a variety of neuropeptides in the hypothalamus, a brain region that also regulates energy homeostasis and feeding behavior. Since circadian rhythms are affected by energy metabolism and feeding condition, we investigated whether changes in feeding regimen would influence sleep/wake parameters and body temperature. We monitored sleep and body temperature across three days of baseline (day 1), fasting (day 2), and refeeding (day 3) conditions under ordinary ambient temperature and employed different refeeding schedules.