• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.12
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• pp.1784-1795
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• 2017

Objective: The study examined the effect of intravenous administration of bacterial endotoxin-lipopolysaccharide (LPS) -on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12). Methods: In both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively. Results: Endotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland. Conclusion: The present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.12
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• pp.1701-1704
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• 2003

Melatonin regulates circadian rhythms and reproduction changes in seasonally reproductive mammals through binding to high-affinity, G-protein-coupled receptors. Small Tail Han sheep that has significant characteristics of high prolificacy and nonseasonal ovulatory activity is an excellent local sheep breed in P. R. China. The exon 2 of the ovine melatonin receptor 1a (MTNR1A) gene was amplified and a uniform fragment of 824 bp was obtained in 150 ewes of Small Tail Han sheep. The 824 bp PCR product was digested with restriction endonucleases Mnl I and Rsa I, and genetic polymorphism was detected by PCR-RFLP. Polymorphic Mnl I site was detected at base position 605 of the exon 2 of the MTNR1A gene. There were two kinds of genotypes in Small Tail Han sheep, AB (303 bp, 236 bp/67 bp) and BB (236 bp/67 bp, 236 bp/67 bp). The results indicated that genotype AA (303 bp, 303 bp) at Mnl I-RFLP site did not exist in non-seasonal estrous Small Tail Han sheep, which suggested that there was an association between genotype AA (303 bp, 303 bp) and reproductive seasonality in sheep. Polymorphic Rsa I site was detected at base position 604 of the exon 2 of the MTNR1A gene. Three kinds of genotypes were found in Small Tail Han sheep, AA (290 bp, 290 bp), AB (290 bp, 267 bp/23 bp) and BB (267 bp/23 bp, 267 bp/23 bp). Least squares means of litter size in the first parity and the second parity for genotype AA (290 bp, 290 bp) at Rsa I-RFLP site were 0.43 and 1.06 more than those for genotype AB (290 bp, 267 bp/23 bp) in Small Tail Han sheep.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.4
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• pp.403-410
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• 2014

The purpose of this study was to examine the anti-depressive effects of OnDam-Tang with addition of Linderae Radix (ODT-L) on the animal model of depression induced by chronic immobilization stress. Depression model was made by chronic immobilization stress for 2 hours for 21 days. And we performed forced swimming test, analysis of the neurotransmitter and immunohistochemical staining, measured expression levels of serotonin in the brain. ODT-L has decreased immobilization time in forced swimming test. ODT-L has increased amount of melatonin in the brain. ODT-L has increased expression levels of serotonin in the brain. ODT-L prevented damage in the hippocampal region. ODT-L has reduced the expression level of CRF receptors in in hippocampus region. These results suggest that ODT-L may have anti-depressive effects on depression.

• Journal of Oriental Neuropsychiatry
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• v.23 no.4
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• pp.11-36
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• 2012

Objectives : Sleep Disorders are very common in clinical stages and there are many reports and papers regarding this subject. I try to understand the present state of sleep research in JON (The Journal of Oriental Neuropsychiatry) for the benefits of clinical practice. Methods : We searched and read every article on JON from 1990 to 2012 and selected ones that are related to Sleep Disorder; then analyzed the data to 5 categories, like literature study, case study, Clinical Data-Analysis study, experimental study, and clinical trial. Results : 1. We Found 41 articles relating to sleep disorder in JON form 1999 to 2012, and there were 9 literature studies, 13 case studies, 13 Clinical Data-Analysis studies, 4 experimental studies, and 2 clinical trials. 2. There were Sa-Am Acupuncture Method, Pharmacopuncture, electroacupuncture, and Auricular acupuncture to treat Sleep Disorder. 3. There were many additional treatments like Purgative Therapy, etc. 4. They reported the ordinary sleep pattern of Soeumin and Soyangin, too. 5. In the experimental study, they reported several herbs, herbal prescription on the expression of melatonin receptors, and Punsimgeimgamibang on insomnia, anxiety, emotionality in rats. 6. There were 2 clinical trials, one for Hwabyung-patient with insomnia by acupuncture treatment and another for insomnia in the elderly by ETF-I program. 7. There were 2 case of other sleep disorder (enuresis, sleepwalking) and 2 literature study of dream. Conclusions : In JON regarding sleep disorder, the majority was due to insomnia. Therefore, we also have to expand our sight into other sleep diseases. We need more clinical trials and experimental researches for the construction of EBM Sleep Disorder in Oriental Neuropsychiatry.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.3
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• pp.277-284
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• 2018

Collagen peptide plays a protective role in skin by increasing the activity of antioxidant, acts like an activator of skin regeneration by positive feedback and is used as a potent candidate for cosmetics or functional food. GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors of both pre- and postsynaptic neuronal processes in vertebrates, is also involved in the synthesis of melatonin and might exert regulatory effects on sleep and reproductive functions. In this study, we investigated the beneficial effect of a mixture of collagen peptide and GABA (J85091900) on skin and sleep condition in woman experiencing sleep disorder. We found that oral supplement with J85091900 significantly decreased the value of Pittsburgh Sleep Quality Index (PSQI), increased sleeping time by 7%, and also improved skin roughness (Ra, Rz, Rt), periorbital wrinkle (Ra, Rt), and skin capacitance in human. These findings indicate that dual strategy with which skin improvement is accomplished using collagen peptide and sleeping well is acquired using GABA could be the novel solution for sleeping beauty by edible cosmetics to improve skin status.