
Shochi NishinoHirosaki University · Department of Biological Science
Shochi Nishino
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Publications
Publications (99)
Introduction
Bathing, especially with hot spring with various mineral compositions, is known to facilitate / improve sleep by warming the body. Artificial carbonated bathing (ACB) is known to keep the body warm too. Previous our study examined that ACB before sleep more specifically affected body temperature and sleep on healthy young subjects. In...
Purpose
Symptomatic narcolepsy is characterized as low orexin (hypocretin) levels (≤ 110 pg/ml) due to neurological diseases. However, we have experienced the cases that show symptoms similar to narcolepsy, complaining of pathological sleepiness even in cases with intermediate orexin levels (110–200 pg/ml). Therefore, we reevaluated the previously...
Introduction
We have been studying sleep facilitation of chloride spring and artificially carbonated spring (ACS). ACS are known to increase peripheral blood flow. We concluded that ACS caused great body temperature change and promoted sleep. On the other hand, ACS are also known to have an effect on the autonomic nervous system, but no one examine...
Introduction
Parasomnias are common in children and decrease in frequency with age. Sleepwalking is one of parasomnias associated with NREM sleep in which a child sits up and crawls or walks around. In contrast, bedwetting, or enuresis, is an involuntary urination during sleep and can occur in all sleep stages. A few small studies have previously r...
Introduction
Insomnia is one of the common sleep problems in Parkinson’s disease (PD). However, pathological mechanisms involved are unknown. MitoPark mice have a selective ablation of midbrain DA neurons by impaired respiratory chain function in DAT-expressing cells and have been validated to show the progressive development of key PD features. We...
Introduction
Next-day residual effects are a common problem with current hypnotic agents. The purpose of the present study was to evaluate the residual effects of the new agent - suvorexant that doesn’t have the muscle relaxation effect - on the physical and cognitive functions of healthy elderly people in the early morning and the day following dr...
Introduction
The human brain changes during development. Cortical gray matter (GM) and superficial white matter (SWM) may be related to certain neurological diseases. Parasomnias such as sleepwalking and bedwetting are common in children and decrease in frequency by age. Although functional and anatomical changes of youth in neuronal circuits have...
Introduction
Delayed sleep phase disorder (DSPD) typically begins in the second decade of life or earlier. DSPD comprises a persistent or recurrent pattern of sleep disturbances, sleep disruption that leads to insomnia and/or excessive daytime sleepiness, and impaired functioning in social, occupational, or other spheres. Three techniques are typic...
Introduction
Chronic sleep disturbance is known to impair dietary metabolisms. Altered dietary metabolisms, such as amino acid level changes, may conversely affect sleep. In accordance with this hypothesis, we reported altered amino acid metabolisms in severe sleep disorders breathing (SDB) patients at Sleep 2016.We have extended the analysis and f...
The symptoms of narcolepsy can occur during the course of other neurological conditions (i.e. symptomatic narcolepsy). We define symptomatic narcolepsy as cases that meet the International Sleep Disorders Narcolepsy Criteria, which are also associated with a significant underlying neurological disorder that accounts for excessive daytime sleepiness...
Introduction
Excessive daytime sleepiness (EDS) can affect 20–50% of patients with Parkinson’s disease (PD), and sudden onset of sleep attacks (SA) in PD behind the wheel often leads to fatal car accidents. Although non-treated PD patients exhibit EDS and SA, SA in PD is often associated with use of DA agonists, especially the recent non-ergot DA D...
Introduction
Recently, several new materials for mattresses become introduced. Although some of these, such as low rebound (or pressure-absorbing) and high rebound mattresses have fairly different characteristics, effects of these mattresses on sleep have never evaluated. In the current study, we have evaluated effects of airweave (a high rebound [...
Sleep influences the cardiovascular, endocrine, and thermoregulatory systems. Each of these systems may be affected by the activity of hypocretin (orexin)-producing neurons, which are involved in the etiology of narcolepsy. We examined sleep in male rats, either hypocretin neuron-ablated orexin/ataxin-3 transgenic (narcoleptic) rats or their wild-t...
Human narcolepsy is a chronic sleep disorder affecting 1:2,000 individuals. The disease is characterized by excessive daytime sleepiness (EDS), cataplexy, and other abnormal manifestations of REM sleep, such as sleep paralysis and hypnagogic hallucinations. Recently, it was discovered that the pathophysiology of (idiopathic) narcolepsy–cataplexy is...
Ubiquitin performs essential roles in a myriad of signalling pathways required for cellular function and survival. Recently, we reported that disruption of the stress-inducible ubiquitin-encoding gene Ubb reduces ubiquitin content in the hypothalamus and leads to adult-onset obesity coupled with a loss of arcuate nucleus neurones and disrupted ener...
(Background and Methods) Two novel hypothalamic neuropeptides, orexin-A (hypocretin-1) and orexin-B (hypocretin-2), have recently been identified. Subsequent studies discovered that a chronic human sleep disorder, namely narcolepsy, is specifically associated with a reduced production of the hypocretin/orexin peptides in the hypothalamus. This orex...
Narcolepsy is a chronic sleep disorder that affects human beings and animals. Up to 17 breeds of dogs are affected sporadically, and familial forms occur in dobermanns, labrador retrievers and dachshunds. These dogs display characteristics strikingly similar to those of human narcolepsy, including cataplexy (a sudden loss of muscle tone in response...
Human narcolepsy is a chronic sleep disorder affecting 1:2,000 individuals [1–3]. The disease is characterized by excessive daytime sleepiness (EDS), cataplexy, and other abnormal manifestations of REM sleep such as sleep paralysis and hypnagogic hallucinations (i.e. narcolepsy tetrad) as well as disturbed night-time sleep (i.e. narcolepsy pentad)...
Central Nervous System (CNS) stimulants used in sleep medicine include amphetamine- like compounds (l- and d-amphetamine and methamphetamine, methylphenidate, pemoline), mazindol, modafinil, some antidepressants with stimulant properties (e.g., buproprion) and caffeine. The effects of most of these drugs on wakefulness is primarily mediated via an...
Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations (HH), and sleep paralysis (SP) (i.e., narcolepsy tetrad) (1,2). A major break through in narcolepsy research was recently made through the identification of hypocretin deficiency in narcolepsy-cataplexy (2–9). Hypocretins...
Current treatments for human narcolepsy are symptomatically based, with primary effects on dopaminergic transmission for stimulants, adrenergic/serotonergic reuptake for anticataplectic antidepressants, and most likely GABA-B agonistic effects for sodium oxybate (GHB) (1–3). Thanks to renewed interest in this area, novel therapies are emerging. The...
The aim of this study was to examine the role of the hypothalamic hypocretin/orexin system in complications of delayed ischemic neuronal deficit (DIND) resulting from symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). CSF hypocretin-1/orexin-A levels were measured in 15 SAH patients. DIND complications occurred in seve...
Four patients with clinically and genetically confirmed Prader-Willi syndrome (PWS) underwent nocturnal polysomnograpy (PSG), multiple sleep latency test (MSLT), human leukocyte antigens (HLA) typing and estimation of cerebrospinal fluid (CSF) hypocretin-1 (Hcrt-1) level to investigate if a role of hypothalamic dysfunction and sleep disturbance mig...
Idiopathic narcolepsy is associated with deficient hypocretin transmission. Narcoleptic symptoms have recently been described in paraneoplastic encephalitis with anti-Ma2 antibodies. The authors measured CSF hypocretin-1 levels in six patients with anti-Ma2 encephalitis, and screened for anti-Ma antibodies in patients with idiopathic narcolepsy. An...
CSF hypocretin-1 was measured in 28 Guillain-Barré syndrome (GBS), 12 Miller-Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (<100 pg/mL). Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller-Fisher syndrome, a...
A two-year-old male chihuahua suffered attacks of muscle weakness and immobility, although it had no family history of paroxysmal attacks. No neurological or blood biochemical abnormalities were recorded when it was first examined. The attacks were typically elicited by stimulation, such as feeding, and a case of sporadic narcolepsy-cataplexy was t...
The hypocretins (1 and 2) have emerged as key regulators of sleep and wakefulness. We developed a high-throughput enzyme immunoassay (EIA) to measure total brain hypocretin levels from large numbers of mice. Hypocretin levels were not altered by circadian time or age. However, significant differences in one or both hypocretin peptides were observed...
Hypocretin-1 levels were increased in evening CSF samples from subjects with restless legs syndrome, indicating altered hypocretin transmission in this sleep disorder. Increases in CSF hypocretin-1 levels were most striking in patients with early-onset restless legs syndrome.
In vitro functional analyses of hypocretin/orexin receptor systems were performed using [(125)I]hypocretin radioreceptor and hypocretin-stimulated [(35)S]GTP gamma S binding assay in cell lines expressing human or canine (wild-type and narcoleptic-mutation) hypocretin receptor 2 (Hcrtr 2). Hypocretin-2 stimulated [(35)S]GTP gamma S binding in human...
To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders.
A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 2...
Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultane...
Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates inc...
Idiopathic narcolepsy usually results from a loss of the hypothalamic neuropeptide orexin (hypocretin), but the cause of secondary narcolepsy resulting from focal brain lesions is unknown. The authors describe a young man who developed narcolepsy after a large hypothalamic stroke. His lesion included much of the hypothalamic region in which orexin...
Cataplexy, an abnormal manifestation of REM sleep atonia, is currently treated with antidepressants. These medications also reduce physiological REM sleep and induce nocturnal sleep disturbances. Because a recent work on canine narcolepsy suggests that the mechanisms for triggering cataplexy are different from those for REM sleep, we hypothesized t...
The effects on cataplexy and daytime sleep of acute and chronic oral administration of CG-3703, a potent TRH analog were assessed in canine narcolepsy. CG-3703 was found to be orally active and to reduce cataplexy (0.25 to 16 mg/kg) and sleep (8 and 16 mg/kg) in a dose-dependent manner. Two-week oral administration of CG-3703 (16 mg/kg) significant...
Using a canine model of narcolepsy and selective DA and NE uptake inhibitors, we have recently shown that DA uptake inhibition promotes wakefulness, while NE uptake inhibition inhibits rapid eye movement sleep and cataplexy. In order to further delineate the respective roles of the dopaminergic and noradrenergic systems in the pharmacological contr...
Amphetamine-like stimulants are commonly used to treat sleepiness in narcolepsy. These compounds have little effect on rapid eye movement (REM) sleep-related symptoms such as cataplexy, and antidepressants (monoamine uptake inhibitors) are usually required to treat these symptoms. Although amphetamine-like stimulants and antidepressants enhance mon...
Narcolepsy is a disabling sleep disorder of unknown aetiology. In humans, the disease is mostly sporadic, with a few familial cases having been reported. In 1973 a sporadic case of narcolepsy was reported in a poodle, and in 1975 familial cases of narcolepsy occurred in dobermanns. As with human narcoleptics, these narcoleptic dogs exhibited excess...
Like human narcoleptics, narcoleptic dogs display cataplexy, fragmented sleep and excessive daytime sleepiness. Cataplexy in dogs can easily be quantified using a simple behavioural bioassay, the Food Elicited Cataplexy Test. In contrast, daytime sleepiness and fragmented sleep are more difficult to measure, as long-term, labour-intensive polygraph...
Canine narcolepsy is a unique experimental model of a human sleep disorder characterized by excessive daytime sleepiness and cataplexy. There is a consensus recognition of an imbalance between cholinergic and catecholaminergic systems in narcolepsy although the underlying mechanisms remain poorly understood. Possible substrates could be an abnormal...
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep-related symptoms, such as cataplexy. The exact pathophysiology underlying the disease is unknown but may involve central cholinergic systems. It is known that the brainstem cholinergic system is activated during REM sleep. Furthermore, RE...
Pharmacological studies using a canine model of narcolepsy have demonstrated that adrenergic rather than serotonergic or dopaminergic uptake inhibition is the primary mode of action of antidepressants on cataplexy, a pathological manifestation of rapid eye movement (REM) sleep atonia that occurs in narcolepsy. This result is in line with the known...
Cataplexy in the narcoleptic canine has been shown to increase after systemic administration of cholinergic agonists. Furthermore, the number of cholinergic receptors in the pontine reticular formation of narcoleptic canines is significantly elevated. In the present study we have investigated the effects of cholinergic drugs administered directly i...
We have demonstrated previously that central noradrenergic mechanisms, especially postsynaptic alpha-1 receptors, are critically involved in the regulation of cataplexy, a pathological manifestation of rapid eye movement sleep atonia in narcolepsy. However, it has been shown recently that alpha-1 receptors constitute a heterogeneous population of b...
Narcolepsy is a genetically determined disorder of sleep characterized by excessive daytime sleepiness and abnormal manifestations of REM sleep that affects both humans and animals. Although its exact pathophysiologic mechanisms remain undetermined, recent experiments have demonstrated that in both humans and canines, susceptibility genes are linke...
Narcolepsy is a sleep disorder characterized by abnormal manifestations of rapid-eye-movement (REM) sleep and excessive daytime sleepiness. Using a canine model of the disease, we found that central D2 antagonists suppressed cataplexy, a form of REM-sleep atonia occurring in narcolepsy, whereas this symptom was aggravated by D2 agonists. The effect...
We have recently established that canine narcolepsy (an autosomal recessive genetic model of the human disorder) is dramatically improved by treatment with alpha 2 antagonists such as yohimbine (Nishino et al: J Pharmacol Exp Ther 253:1145-1152, 1990). To further investigate the role of alpha 2 adrenoceptors in narcolepsy, receptors labeled with [3...
Narcolepsy is a disorder characterized by excessive daytime sleepiness, a disturbed sleep pattern, and in many cases by sudden attacks of partial or complete loss of muscle tone (cataplexy) induced by emotional stimulation. Both the sleep attacks and the cataplectic attacks are not only very disabling for the patients but in some situations (e.g.,...
Recent experiments have demonstrated that pharmacological activation of central noradrenergic systems by monoaminergic stimulators or uptake blockers or through the stimulation of alpha-1 adrenergic receptors improved cataplexy, a major symptom of narcolepsy. In order to further the understanding of the control of cataplexy by noradrenergic mechani...
The effects of intravenous administration of prostaglandins (PGs) were investigated in genetically narcoleptic Doberman pinschers. The treatment of narcoleptic dogs with PGE2 and PGE2 methyl ester, but not PGD2 and PGD2 methyl ester, induced a dose-dependent reduction of canine cataplexy, a dissociated manifestation of rapid-eye-movement sleep. The...
Salivary prostaglandin concentrations were determined in 42 patients with major depressive disorder, 16 patients with minor depressive disorder, and 39 healthy control subjects. The diagnoses were made according to the Research Diagnostic Criteria. The patients with major depressive disorder had higher salivary prostaglandin concentrations than the...
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