Non-rapid Eye Movement Sleep Activity Research Articles

GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice

Sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed mechanism is far from understood. Here, we found that glutamic acid decarboxylase 67-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTAGad67+ promoted NREM sleep with higher delta power whereas optogenetic inhibition of these induced prompt arousal from NREM sleep, even under highly somnolescent conditions, but not from REM sleep. VTAGad67+ showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTAGad67+ directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTAGad67+ terminals in the LH promoted NREM sleep. Taken together, we revealed that VTAGad67+ play an important role in the regulation of NREM sleep.

Medicinal Plants for Management of Insomnia: A Systematic Review of Animal and Human Studies.

Insomnia is one of the most troubling sleep disorders and can be characterized by an inability to fall asleep and/or inadequate sleep duration and/or waking up multiple times during the night. Herbal medicine has been used to treat a range of sleep disorders for centuries. This study aimed to review medicinal plants investigated experimentally or clinically for sleep disorders, as well as their potential mechanisms of action and active components. Electronic databases and literature were systematically investigated to assess all in vitro and in vivo trials and clinical evidence of the efficacy and potential mechanisms of actions playing major roles in sleep induction or insomnia treatment. Among many herbal studies and trials on insomnia, some showed no significant difference between herbal remedies and placebos. While others showed improvements in sleep parameters (sleep latency, total sleep, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep duration, delta activity in NREM sleep, wakefulness anxiety-associated insomnia). In this study, in vitro, animal, and clinical studies investigating a variety of herbal treatments for insomnia were systematically reviewed. The mechanisms of action of herbal medicines in treating insomnia are mainly related to gamma-aminobutyric acid (GABA)-synthesizing and GABA-metabolizing enzymes that influenced sleep outcomes. Overall, herbal remedies were not associated with more benefits than nonbenzodiazepines, although side effects were less. The results suggest that herbs have some benefits in improving the quantity and quality of sleep and could be a promising alternative therapy.

Medicinal Plants for Management of Insomnia: A Systematic Review of Animal and Human Studies


 Insomnia is one of the most troubling sleep disorders and can be characterized by an inability to fall asleep and/or inadequate sleep duration and/or waking up multiple times during the night. Herbal medicine has been used to treat a range of sleep disorders for centuries. This study aimed to review medicinal plants investigated experimentally or clinically for sleep disorders, as well as their potential mechanisms of action and active components. Electronic databases and literature were systematically investigated to assess all in vitro and in vivo trials and clinical evidence of the efficacy and potential mechanisms of actions playing major roles in sleep induction or insomnia treatment. Among many herbal studies and trials on insomnia, some showed no significant difference between herbal remedies and placebos. While others showed improvements in sleep parameters (sleep latency, total sleep, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep duration, delta activity in NREM sleep, wakefulness anxiety-associated insomnia). In this study, in vitro, animal, and clinical studies investigating a variety of herbal treatments for insomnia were systematically reviewed. The mechanisms of action of herbal medicines in treating insomnia are mainly related to gamma-aminobutyric acid (GABA)-synthesizing and GABA-metabolizing enzymes that influenced sleep outcomes. Overall, herbal remedies were not associated with more benefits than non-benzodiazepines, although side effects were less. The results suggest that herbs have some benefits in improving the quantity and quality of sleep and could be a promising alternative therapy. [GMJ.2019;8:e1085]

Medicinal Plants for Management of Insomnia: A Systematic Review of Animal and Human Studies

Insomnia is one of the most troubling sleep disorders and can be characterized by an inability to fall asleep and/or inadequate sleep duration and/or waking up multiple times during the night. Herbal medicine has been used to treat a range of sleep disorders for centuries. This study aimed to review medicinal plants investigated experimentally or clinically for sleep disorders, as well as their potential mechanisms of action and active components. Electronic databases and literature were systematically investigated to assess all in vitro and in vivo trials and clinical evidence of the efficacy and potential mechanisms of actions playing major roles in sleep induction or insomnia treatment. Among many herbal studies and trials on insomnia, some showed no significant difference between herbal remedies and placebos. While others showed improvements in sleep parameters (sleep latency, total sleep, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep duration, delta activity in NREM sleep, wakefulness anxiety-associated insomnia). In this study, in vitro, animal, and clinical studies investigating a variety of herbal treatments for insomnia were systematically reviewed. The mechanisms of action of herbal medicines in treating insomnia are mainly related to gamma-aminobutyric acid (GABA)-synthesizing and GABA-metabolizing enzymes that influenced sleep outcomes. Overall, herbal remedies were not associated with more benefits than non-benzodiazepines, although side effects were less. The results suggest that herbs have some benefits in improving the quantity and quality of sleep and could be a promising alternative therapy. [GMJ.2019;In press:e1085]

Baclofen and gamma-hydroxybutyrate differentially altered behavior, EEG activity and sleep in rats

Objectives: Animal and human studies have shown that sleep may have an impact on functional recovery after brain damage. Baclofen (Bac) and gamma-hydroxybutyrate (GHB) have been shown to induce physiological sleep in humans, however, their effects in rodents are unclear. The aim of this study is to characterize sleep and electroencelphalogram (EEG) after Bac and GHB administration in rats. We hypothesized that both drugs would induce physiological sleep.Methods: Adult male Sprague-Dawley rats were implanted with EEG/electromyogram (EMG) electrodes for sleep recordings. Bac (10 or 20mg/kg), GHB (150 or 300mg/kg) or saline were injected 1h after light and dark onset to evaluate time of day effect of the drugs. Vigilance states and EEG spectra were quantified.Results: Bac and GHB induced a non-physiological state characterized by atypical behavior and an abnormal EEG pattern. After termination of this state, Bac was found to increase the duration of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep (∼90 and 10min, respectively), reduce sleep fragmentation and affect NREM sleep episode frequency and duration (p<0.05). GHB had no major effect on vigilance states. Bac drastically increased EEG power density in NREM sleep in the frequencies 1.5–6.5 and 9.5–21.5Hz compared to saline (p<0.05), while GHB enhanced power in the 1–5-Hz frequency band and reduced it in the 7–9-Hz band. Slow-wave activity in NREM sleep was enhanced 1.5–3-fold during the first 1–2h following termination of the non-physiological state. The magnitude of drug effects was stronger during the dark phase.Conclusion: While both Bac and GHB induced a non-physiological resting state, only Bac facilitated and consolidated sleep, and promoted EEG delta oscillations thereafter. Hence, Bac can be considered a sleep-promoting drug and its effects on functional recovery after stroke can be evaluated both in humans and rats.

Sex differences and the effect of gaboxadol and zolpidem on EEG power spectra in NREM and REM sleep

Hypnotics that interact with the GABA(A) receptor have marked effects on the electroencephalogram (EEG) during sleep. It is not known whether the effects of hypnotics on EEG power spectra differ between the sexes. The effects of 5, 10 and 15 mg of gaboxadol (GBX) and 10 mg of zolpidem (ZOL) on EEG power spectra were assessed in a randomized, double-blind, placebo-controlled, 5-way cross-over design study using a phase-advance model of transient insomnia. Sleep stage specific EEG power spectra were computed in 36 men and 45 women. GBX enhanced power density in delta and theta activity in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and suppressed sleep spindle activity in NREM sleep. The increase of delta and theta activity in NREM and REM sleep was significantly larger for women than for men but the suppression of spindle activity did not differ between the sexes. After ZOL administration, no sex differences were observed in the reduction of delta and theta activity in NREM sleep, but the increase in sleep spindle activity in NREM sleep was greater in women than in men. These sex dependent and differential effects of GBX and ZOL may be related to their differential affinity for GABA(A) receptor subtypes and their modulation by neurosteroids.

Sex Differences in Delta and Alpha EEG Activities in Healthy Older Adults

To examine sex effects on sleep stages and electroencephalogram (EEG) spectral power in older adults. Sleep was polygraphically recorded for 2 consecutive nights, and blood was sampled during the last 24 hours. The University of Chicago Clinical Research Center. Two groups of healthy nonobese older subjects: 10 men (59 +/- 2 years), and 10 postmenopausal women (63 +/- 2 years). N/A. A spectral analysis of the EEG was performed in the delta and alpha bands. There were no sex differences in sleep stages. Blood sampling resulted in reductions of total sleep time, sleep maintenance, slow-wave sleep, and absolute delta activity that were all larger in women than in men. In absolute values, delta and alpha activities in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were higher in women than in men, but, for delta activity, the sex differences were larger in REM than in NREM sleep. In women, but not in men, absolute delta activity in REM was decreased during blood sampling and was strongly correlated with absolute delta activity in NREM. Delta activity in REM did not dissipate across the night in either group. When normalized for the activity in REM sleep, the sex difference in delta activity in NREM sleep was reversed, with lower activity in women. Sex differences in sleep EEG variables are present in older adults. When normalized, delta activity in older women is lower than in older men, which may be more consistent with sex differences in subjective complaints, in fragility of sleep in the presence of environmental disturbances, and in the relationship to growth-hormone release.

Effects of alpha-MSH on sleep, behavior, and brain temperature: interactions with IL 1.

Changes in rabbit sleep-wake activity, brain temperature (Tbr), and behavior were studied after intracerebroventricular injections of a putative endogenous antipyretic, alpha-melanocyte-stimulating hormone (alpha-MSH), and of an endogenous pyrogen, interleukin 1 (IL 1-beta). alpha-MSH (0.1-50.0 micrograms) dose dependently increased wakefulness (W) and decreased Tbr, non-rapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). NREMS was more sensitive than REMS to the suppressive effects of low alpha-MSH doses. EEG slow-wave activity in NREMS decreased after alpha-MSH treatment. alpha-MSH elicited stretching, yawning, and signs of sexual excitation. IL 1 (20 and 40 ng) induced fever and excess NREMS. alpha-MSH administered 30 min after IL 1 (40 or 20 ng IL 1 + 0.1, 0.5, or 5.0 micrograms alpha-MSH) significantly attenuated IL 1-induced fever and excess NREMS. IL 1 failed to alter the behavioral effects of alpha-MSH. Despite alpha-MSHs effect on rabbit behavior, total motor activity time did not increase, indicating that increased W after alpha-MSH cannot be attributed to behavioral activation. These results suggest that, besides acting as an endogenous antipyretic, alpha-MSH might be involved in regulation of IL 1-induced sleep.

Ulcerative Colitis

<h3>Abstract</h3> The daily sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed neural circuitry mediating sleep is far from understood. Here, we found that glutamic acid decarboxylase 67 (Gad67)-positive GABAergic neurons in the ventral tegmental area (VTA_Gad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTA_Gad67+ neurons project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH) and dorsal raphe nucleus. Chemogenetic activation of VTA_Gad67+ neurons promoted NREM sleep with higher delta power whereas optogenetic inhibition of these neurons induced prompt arousal from NREM sleep under highly somnolescent conditions, but not during REM sleep. <i>In vivo</i> fiber photometry recordings revealed that VTA_Gad67+ neurons showed the highest population activity in NREM sleep and the lowest activity in REM sleep. Acute brain slice electrophysiology combined with optogenetics revealed that VTA_Gad67+ neurons directly innervate and inhibit wake-promoting orexin/hypocretin neurons in the LH by releasing GABA. Taken together, we reveal that VTA_Gad67+ neurons play a crucial role in the regulation of NREM sleep.