scholarly journals GABAA Receptor-Mediated Sleep-Promoting Effect of Saaz–Saphir Hops Mixture Containing Xanthohumol and Humulone

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7108
Author(s):  
Byungjick Min ◽  
Yejin Ahn ◽  
Hyeok-Jun Cho ◽  
Woong-Kwon Kwak ◽  
Hyung Joo Suh ◽  
...  

Hops contain flavonoids that have sedative and sleep-promoting activities such as α-acid, β-acid, and xanthohumol. In this study, the sleep-enhancing activity of a Saaz–Saphir hops mixture was measured. In the caffeine-induced insomnia model, the administration of a Saaz–Saphir mixture increased the sleep time compared to Saaz or Saphir administration alone, which was attributed to the increase in NREM sleep time by the δ-wave increase. Oral administration of the Saaz–Saphir mixture for 3 weeks increased the γ-amino butyric acid (GABA) content in the brain and increased the expression of the GABAA receptor. As the GABA antagonists picrotoxin and bicuculline showed a decrease in sleep activity, it was confirmed that the GABAA receptor was involved in the Saaz–Saphir mixture activity. In addition, the GABAA receptor antagonist also reduced the sleep activity induced by xanthohumol and humulone contained in the Saaz–Saphir mixture. Therefore, xanthohumol and humulone contained in the Saaz–Saphir mixture showed sleep-promoting activity mediated by the GABAA receptors. The mixture of the Saaz and Saphir hop varieties may thus help mitigate sleep disturbances compared to other hop varieties.

1996 ◽  
Vol 270 (6) ◽  
pp. C1726-C1734 ◽  
Author(s):  
M. Shimura ◽  
N. Harata ◽  
M. Tamai ◽  
N. Akaike

The gamma-aminobutyric acid (GABA)-induced response was investigated in acutely dissociated suprachiasmatic nucleus (SCN) neurons of 11- to 14-day-old rats, under the voltage-clamp condition of nystatin-perforated patch recording. At a holding potential of -40 mV, application of GABA induced inward currents in a concentration-dependent manner. Pentobarbital and 5 beta-pregnan-3 alpha-ol-20-one (pregnanolone) similarly induced inward currents. GABA-induced inward currents were suppressed in a concentration-dependent manner by pretreating neurons with a GABAA receptor antagonist, bicuculline. Bicuculline (3 x 10(-6) M) shifted the concentration-response curve of GABA to the left in a competitive manner. Reversal potential of the GABA response (EGABA) was -3.4 +/- 0.7 mV, close to the theoretical Cl- equilibrium potential of -4.1 mV. Pretreating SCN neurons with diazepam, pentobarbital, and pregnanolone enhanced the 3 x 10(-6) M GABA response. Diazepam (3 x 10(-8) M), pentobarbital (3 x 10(-5) M), and pregnanolone (10(-7) M) shifted the concentration-response curve of GABA to the left without changing the maximal amplitude of GABA responses. EGABA in the presence of diazepam, pentobarbital, or pregnanolone was the same as that in their absence. These results show that the GABA response in acutely dissociated SCN neurons is mediated by the GABAA receptor. Because the GABAA receptor of SCN neurons is allosterically augmented by diazepam, pentobarbital, and pregnanolone, similarly as in other regions of the central nervous system, the present study opens up ways to functionally modulate the GABAA receptors in SCN.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xiang-Shan Yuan ◽  
Lu Wang ◽  
Hui Dong ◽  
Wei-Min Qu ◽  
Su-Rong Yang ◽  
...  

Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A2AR neurons. In addition, chemogenetic inhibition of striatal A2AR neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A2AR neuron/GPe PV neuron circuit in sleep control.


2020 ◽  
Vol 36 (10) ◽  
pp. 1137-1146 ◽  
Author(s):  
Xiang Feng ◽  
Hui-Ying Zhao ◽  
Yu-Jin Shao ◽  
Hui-Fang Lou ◽  
Li-Ya Zhu ◽  
...  

Abstract Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.


Author(s):  
Rita A. Costa ◽  
Zélia Velez ◽  
Peter C. Hubbard

Exposure to high PCO2/low pH seawater induces behavioural alterations in fish; a possible explanation for this is a reversal of Cl−/HCO3− currents through GABAA receptors (the GABAA receptor theory). However, the main evidence for this is that gabazine, a GABAA receptor antagonist, reverses these effects when applied to the water, assuming that exposure to systems other than the CNS would be without effect. Here, we show the expression of both metabotropic and ionotropic GABA receptors, and the presence of GABAA receptor protein, in the olfactory epithelium (OE) of gilthead seabream. Furthermore, exposure of the OE to muscimol (a specific GABAA receptor agonist) increases or decreases the apparent olfactory sensitivity to some odorants. Thus, although the exact function of GABAA receptors in the OE is not yet clear, this may complicate the interpretation of studies wherein water-borne gabazine is used to reverse the effects of high CO2 levels on olfactory-driven behaviour in fish.


2018 ◽  
Vol 32 (1) ◽  
pp. 24-30
Author(s):  
Hayun Choi ◽  
Jahyun Jeong ◽  
Heejun Kim ◽  
Chuljin Shin ◽  
In-Young Yoon

Objective: In elderly patients, women have better qualities of sleep than men in objective parameters; however, women subjectively complain more about sleep disturbances than men. We performed visual scoring and spectral analysis of sleep electroencephalograms to explain these gender differences in the degree of arousal, the most representative marker in insomnia. Methods: A total of 354 participants (≥60 years old) were recruited from a Korean community underwent nocturnal polysomnography (NPSG). A Fast Fourier transform was used for the spectral analysis of the NPSG data. Relative power was calculated as absolute power of each band divided by total absolute power. Difference in total sleep time (D_TST) is obtained by subtracting the total sleep time reported in Pittsburgh Sleep Quality Index (PSQI) from the TST measured by the NPSG. Results: A total of 75 participants (women, 51) were finally analyzed. Women had higher PSQI, longer sleep latencies, sleep inefficiencies, and daytime dysfunctions compared to men. The percentage of stage 1 sleep was higher in men versus in women, whereas percentage of stage 3 sleep was higher in women than in men ( P = .001; P = .001). Women had higher relative alpha and beta powers than men during nonrapid eye movement (NREM) sleep ( P = .017; P = .015). During NREM sleep, beta power was negatively correlated with D_TST ( R = −0.250, P = .033), and relative alpha power in stage 3 sleep was positively correlated with sleep latency in PSQI ( R = 0.267, P = .022). Conclusion: Spectral analysis showed that women had more disturbed sleep than men. The result from the spectral analysis may explain hyperarousal in elderly women.


2021 ◽  
Vol 10 (1) ◽  
pp. 47-54
Author(s):  
Lisda Amalia ◽  

Stroke is a condition when a person has a sudden neurological deficit caused by a disruption in the blood vessels of the brain. About 21-77% of stroke patients have sleep disorders that occur after a stroke. The sleep cycle is regulated by the brain and strokes can cause sleep disturbances due to abnormalities that can occur in the brain structures that regulate sleep. Post Stroke Sleep Disoder (PSSD) is the most common symptom after stroke. Sleep disorders after stroke include Sleep Disordered Breathing (SDB), insomnia, circadian rhythm sleep disturbance, hypersomnia, parasomnia and sleep-related movement disorders. Sleep has many benefits, one of which is the restoration of physical and mental functions, the consolidation of memory and improving the learning ability of a person both motorically and sensitively. Other studies have also shown a correlation between electrographic sleep time and cognitive function of stroke patients during recovery. Another experimental study also indicated that sleep disorders can increase the expression of neurocans, which are genes that inhibit nerve growth. Sleep disorders in stroke patients can reduce the efficiency and effectiveness of stroke rehabilitation


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 970
Author(s):  
Kyungae Jo ◽  
Singeun Kim ◽  
Yejin Ahn ◽  
Hyung Joo Suh

This study investigated the effect of ethanol-extracted green lettuce leaf (GLE) on sleep behavior in physical stress-induced invertebrate and vertebrate models. In Drosophila melanogaster, the group that experienced vibration stress showed decreased sleep time compared to the no-vibration-stress control group, but the GLE treatment group recovered this lost sleep time. The GLE group also recovered the gene expression of downregulated superoxide dismutase induced by vibration stress conditions. According to electroencephalography analysis of rats, non-rapid eye movement (NREM) sleep significantly decreased with a decrease in sleep time for the group in which immobilization stress was induced. In the GLE group (120 mg/kg), the change in sleep pattern caused by stress was restored, and NREM sleep increased by 68.8%, improving overall sleep quality. In addition, GLE upregulated the expression levels of oxidation-related factors and γ-aminobutyric acid (GABAA) receptor. Quercetin-3-glucuronide (Q3G) was evaluated as a sleep-promoting active substance contained in GLE using the pentobarbital-induced sleep test and showed the effect of prolonged sleep time. Q3G inhibited [3H]-flumazenil binding in a concentration-dependent manner with GLE. Taken together, the results indicate that GLE effectively binds to the GABAA receptor to promote sleep, demonstrating the potential of Q3G as an active substance.


2007 ◽  
Vol 177 (4S) ◽  
pp. 86-87
Author(s):  
Yosuke Matsuta ◽  
Aniwar Yusup ◽  
Masaharu Nakai ◽  
Kazuya Tanase ◽  
Yoshitaka Aoki ◽  
...  
Keyword(s):  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jing Guang ◽  
Halen Baker ◽  
Orilia Ben-Yishay Nizri ◽  
Shimon Firman ◽  
Uri Werner-Reiss ◽  
...  

AbstractDeep brain stimulation (DBS) is currently a standard procedure for advanced Parkinson’s disease. Many centers employ awake physiological navigation and stimulation assessment to optimize DBS localization and outcome. To enable DBS under sedation, asleep DBS, we characterized the cortico-basal ganglia neuronal network of two nonhuman primates under propofol, ketamine, and interleaved propofol-ketamine (IPK) sedation. Further, we compared these sedation states in the healthy and Parkinsonian condition to those of healthy sleep. Ketamine increases high-frequency power and synchronization while propofol increases low-frequency power and synchronization in polysomnography and neuronal activity recordings. Thus, ketamine does not mask the low-frequency oscillations used for physiological navigation toward the basal ganglia DBS targets. The brain spectral state under ketamine and propofol mimicked rapid eye movement (REM) and Non-REM (NREM) sleep activity, respectively, and the IPK protocol resembles the NREM-REM sleep cycle. These promising results are a meaningful step toward asleep DBS with nondistorted physiological navigation.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A29-A30
Author(s):  
Michael Goldstein ◽  
Monika Haack ◽  
Janet Mullington

Abstract Introduction Prior research has reported NREM spectral EEG differences between individuals with insomnia and good-sleeper controls, including elevated high-frequency EEG power (beta/gamma bands, ~16-50Hz) and, to a lesser extent, elevations in sleep spindle parameters. However, the mechanisms driving these differences remain unclear. Harmonics have been observed in EEG data as spectral peaks at multiples of a fundamental frequency associated with an event (e.g., for a 14Hz spindle, the 2nd harmonic is expected to be a peak at 28Hz). Thus far, there has been very limited application of this idea of spectral harmonics to sleep spindles, even though these patterns can indeed be seen in some existing literature. We sought to build on this literature to apply spectral harmonic analysis to better understand differences between insomnia and good sleepers. Methods 15 individuals with insomnia disorder (DSM-5 criteria, 13 female, age 18–32 years) and 15 good-sleeper controls (matched for sex, age, and BMI) completed an overnight polysomnography recording in the laboratory and subsequent daytime testing. Insomnia diagnosis was determined by a board-certified sleep specialist, and exclusion criteria included psychiatric history within past 6 months, other sleep disorders, significant medical conditions, and medications with significant effects on inflammation, autonomic function, or other psychotropic effects. Results Consistent with prior studies, we found elevated sleep spindle density and fast sigma power (14-16Hz). Despite no difference in beta or gamma band power when averaged across NREM sleep, time-frequency analysis centered on the peaks of detected spindles revealed a phasic elevation in spectral power surrounding the 28Hz harmonic peak in the insomnia group, especially for spindles coupled with slow waves. We also observed an overall pattern of time-locked delay in the 28Hz harmonic peak, occurring approximately 40 msec after spindle peaks. Furthermore, we observed a 42Hz ‘3rd harmonic’ peak, not yet predicted by the existing modeling work, which was also elevated for insomnia. Conclusion In conjunction with existing mathematical modeling work that has linked sleep spindle harmonic peaks with thalamic relay nuclei as the primary generators of this EEG signature, these findings may enable novel insights into specific thalamocortical mechanisms of insomnia and non-restorative sleep. Support (if any) NIH 5T32HL007901-22


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