Antisense oligonucleotide therapeutic approach for Timothy syndrome.

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A.

Evaluation of the benefits of neutral bicarbonate ionized water baths in an open-label, randomized, crossover trial.

We previously demonstrated that neutral bicarbonate ionized water (NBIW) bathing enhances blood flow by bicarbonate ions and described the underlying mechanism. However, additional clinical investigation was warranted to investigate the efficacy of NBIW bathing. Hence, we performed a randomized, open-label, crossover trial to examine the effects of NBIW bathing on mental stress, sleep, and immune function.

Eurycoma longifolia (Tongkat Ali) enhances wakefulness during active periods but facilitates sleep during resting periods in C57BL/6 mice.

The effects of the Eurycoma longifolia (also known as Tongkat Ali [TA]) on sleep and wakefulness was evaluated in C57BL/6 mice. While TA has been used as an aphrodisiac in males, it exhibits various pharmacological effects. The most notable effect observed with TA was wake-enhancement during the second half of the active period, accompanied by significant elevations in core body temperature (CBT).

BMAL1 loss in oligodendroglia contributes to abnormal myelination and sleep.

Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time-of-day dependent. Knockout of Bmal1 in mouse OPCs during development disrupts the expression of genes associated with circadian rhythms, proliferation, density, morphology, and migration, leading to changes in OPC dynamics in a spatiotemporal manner.

Analysis of the Effects of Known Sleep-Support Supplements in Relation to Life Habits, Sleep Conditions, and Sleep Problems.

Sleep is a crucial component of health, and insomnia is among the most common and vexing of life-habit-related disorders. While dietary sleep-support supplements can improve sleep, choosing an effective dietary supplement can be challenging for users due to the wide variety of options available and the varying effects experienced by different individuals. In this study, to identify new criteria for estimating the effects of dietary supplements, we examined the relationships among the dietary supplements, the pre-conditions (PCs; defined as the life habits and sleep conditions before supplementation), and the sleep problems of subjects before supplementation.

Changes in sleep profile on exposure to sodium chloride and artificially carbonated springs: a pilot study.

[Purpose] Herein, we aimed to investigate the effects of bathing in a sodium chloride spring and an artificially carbonated spring on core body temperature and electroencephalograms, to assess whether the springs facilitate sleep. [Participants and Methods] This randomized, controlled, crossover study evaluated the effects of a sodium chloride spring, an artificially carbonated spring, a plain hot bath, and no bath on sleep. The subjective evaluations and recording of temperature were performed before/after bathing at 40 °C for 15 min at 22:00 h, before nocturnal sleep (0:00-7:00 h), and after the participants (n=8) woke up in the morning.

Comparison of Solriamfetol and Modafinil on Arousal and Anxiety-Related Behaviors in Narcoleptic Mice.

Wake-promoting agents are used for the management of excessive daytime sleepiness caused by narcolepsy. Clinical and preclinical data suggests that solriamfetol, a novel dopamine and norepinephrine reuptake inhibitor, is a promising therapeutic option for excessive daytime sleepiness. We provide the first head-to-head comparison of in vivo efficacy between modafinil and solriamfetol in narcoleptic mice.

Influences of sleep and lifestyle factors on the risk for covid-19 infections, from internet survey of 10,000 Japanese business workers.

We conducted an internet survey to assess sociodemographic variables, lifestyle factors, sleep problems, and comorbidities for sleep apnea syndrome (SAS) in COVID-19 and influenza (FLU) infections. Data from 10,323 workers (50.0% male) were analyzed.

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).

Maturation and circuit integration of transplanted human cortical organoids.

Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits.

Pharmacologic Management of Excessive Daytime Sleepiness.

Excessive daytime sleepiness (EDS) is defined as "irresistible sleepiness in a situation when an individual would be expected to be awake, and alert." EDS has been a big concern not only from a medical but also from a public health point of view. Patients with EDS have the possibility of falling asleep even when they should wake up and concentrate, for example, when they drive, play sports, or walk outside.

Residual effects of low dose of suvorexant, zolpidem, and ramelteon in healthy elderly subjects: A randomized double-blind study.

Introduction: Current hypnotic agents have next-day residual effects. The new orexin antagonist, suvorexant, has little muscle relaxation effect on the physical and cognitive function in the following morning and daytime. In this study, the effects of suvorexant, zolpidem, ramelteon and placebo in elderly subjects were evaluated.

Brain Mast Cells in Sleep and Behavioral Regulation.

The function of mast cells in the brain for the mediation of neurobehavior is largely unknown. Mast cells are a heterogeneous population of granulocytic cells in the immune system. Mast cells contain numerous mediators, such as histamine, serotonin, cytokines, chemokines, and lipid-derived factors.

A rare genetic variant in the cleavage site of prepro-orexin is associated with idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is a rare, heterogeneous sleep disorder characterized by excessive daytime sleepiness. In contrast to narcolepsy type 1, which is a well-defined type of central disorders of hypersomnolence, the etiology of IH is poorly understood. No susceptibility loci associated with IH have been clearly identified, despite the tendency for familial aggregation of IH.

Altered responses of end-expiratory lung volume and upper airway patency to body posture in diet-induced obese mice.

Objective: Although both obesity and body posture are important factors affecting end-expiratory lung volume (EELV) and upper airway patency, the influence of those factors on EELV and the association between EELV and upper airway calibers are still unknown in mice. This study examined such interaction effects in obese mice to test the hypothesis that obese mice have decreased EELV accompanied by structural alterations of the upper airway.

Methods: A high-resolution in vivo micro-computed tomography was utilized to scan anesthetized lean and diet-induced obese mice in the prone and supine positions, followed by quantifying lung volume and analyzing upper airway morphology.

Sake yeast induces the sleep-promoting effects under the stress-induced acute insomnia in mice.

Sleep deprivation induces adverse effects on the health, productivity, and performance. The individuals who could not get enough sleep temporarily experience the symptoms of an induced acute insomnia. This study investigated the efficacy of sake yeast in treatment of acute insomnia in mice.

Genetic and demographic predisposing factors associated with pediatric sleepwalking in the Philadelphia Neurodevelopmental Cohort.

Objectives: Sleepwalking is a parasomnia associated with non-rapid eye movement (NREM) sleep and is formally diagnosed using polysomnography (PSG). However, PSG are difficult to perform on children or adolescents due to needed compliance. To understand this condition in youth, few studies have been conducted on a large cohort of youths with a diverse distribution of ages and races to characterize it better in the absence of PSG.

Advances in the pharmacological management of non-24-h sleep-wake disorder.

: Melatonin, a hormone that regulates circadian rhythms and the sleep-wake cycle, is produced mainly during the dark period in the pineal gland and is suppressed by light exposure. Patients with non-24-h sleep-wake disorder (non-24) fail to entrain the master clock with the 24-h light-dark cycle due to the lack of light perception to the suprachiasmatic nucleus typically in totally blind individuals or other organic disorders in sighted individuals, causing a progressive delay in the sleep-wake cycle and periodic insomnia and daytime sleepiness.: Herein, the authors review the pharmacological therapies including exogenous melatonin and melatonin receptor agonists for the management of non-24.

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.

Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome.

A high prevalence of obstructive sleep apnea (OSA) has been reported in Down syndrome (DS) owing to the coexistence of multiple predisposing factors related to its genetic abnormality, posing a challenge for the management of OSA. We hypothesized that DS mice recapitulate craniofacial abnormalities and upper airway obstruction of human DS and can serve as an experimental platform for OSA research. This study, thus, aimed to quantitatively characterize the upper airway as well as craniofacial abnormalities in Dp(16)1Yey (Dp16) mice.

Neuronal defects in a human cellular model of 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids.

Evaluations of effects of sleep surfaces on athletic performance in youth.

We recently demonstrated that sleeping on high rebound [HR] mattress toppers induced a continuous and more rapid decline in core body temperature compared to low rebound [LR] mattress toppers during the initial phase of nocturnal sleep in young healthy volunteers. HR toppers are characterized by their supportive feel and high breathability whereas LR toppers are pressure-absorbing. In the current study, we evaluated effects of HR mattress toppers on objectively-(actigraphy) and subjectively-(questionnaires) evaluated sleep, vigilance (psychomotor vigilance test), and athletic performance (40-m sprint time, long jump distance, and star drill time) in youth male athletes age 10-19, in two sessions: fifty-one subjects in 2013 (study I) and 23 subjects in 2014 (study II).