• Archives of Pharmacal Research
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• 제22권1호
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• pp.35-43
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• 1999

Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors has been reported to induce excitatoxicity which can be characterized by neuronal damage and formation of reactive oxygen free radicals. Neuroprotective effect of melatonin against KA-induced excitotoxicity have been documented in vitro and in vivo. It is, however, not clear whether melationin is also neuroportective against excitotoxicity mediated by NMDA receptors. In the present work, we tested the in vivo protective effects of striatally infused melatonin against the oxidative stress and neuronal damage induced by the injection of KA and NMDA receptors into the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel cannule with melatonin fused inside the tip were placed bilaterally in the rat brain one week prior to intrastriatal injection of glutamate receptor subtype agonists. Melatonin showed protective effects against the elevation of lipid peroxidation induced by either KA or NMDA and recovered Cu, Zn-superoxide dismutase activities reduced by both KA and NMDA into the control level. Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal damage assessed by the determination of choline acetyltransferase activity in striatal monogenages and by microscopic observation of rat brain section stained with cresyl violet. The protective effects of melatonin are comparable to those of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively. It is suggested that melatonin could protect against striatal oxidative damages mediated by glutamate receptors, both non-NMDA and NMDA receptors.

• 한국발생생물학회지:발생과생식
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• 제17권1호
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• pp.45-53
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• 2013

The action of melatonin within the body of animals is known to be mediated by melatonin receptors. Three different types of melatonin receptors have been identified so far in fish. However, which of these are specifically involved in puberty onset is not known in fish. We cloned and analyzed the sequence of melatonin receptor 1a (mel 1a) gene in Nile tilapia Oreochromis niloticus. In addition, we examined the tissue distribution of gene expressions for three types of receptors, mel 1a, 1b and lc and investigated which of them is involved in the onset of puberty by comparing their expression with that of gonadotropin-releasing hormone receptor I (GnRHr I) gene using quantitative real-time PCR from 1 week post hatch (wph) to 24 wph. The mel 1a gene of Nile tilapia consisted of two exons and one bulky intron between them. Mel 1a gene was found to be highly conserved gene showing high homology with the corresponding genes from different teleost. All three types of melatonin receptor genes were expressed in the brain, eyes and ovary in common. Expression of mel 1a gene was the most abundant and ubiquitous among 3 receptors in the brain, liver, gill, ovary, muscle, eye, heart, intestine, spleen and kidney. Mel 1b and mel 1c genes were, however, expressed in fewer tissues at low level. During the development post hatch, expressions of both mel 1a and GnRHr I genes significantly increased at 13 wph which was close to the putative timing of puberty onset in this species. These results suggest that among three types of receptors mel 1a is most likely associated with the action of melatonin in the onset of puberty in Nile tilapia.

• 동의신경정신과학회지
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• 제18권1호
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• pp.15-36
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• 2007

Objective : This study was to investigate the effects of several herbs on the levels of MT1 and MT2 melatonin receptors Methods: It was investigated the effects of several herbs such as WEDL, WEZV, WEFO, WEOC on the levels of MT1 and MT2 melatonin receptors using C6 glial cell model. ${\beta}-estradiol$ treatment, as a positive control group, under non-cytotoxic condition. Results : 1. The water extracts of Dimocarpus long (WEDL) induced the levels of MT2 melatonin receptor expression in a concentration-dependent manner without altering the levels of MT1 melatonin receptor expression. 2. The treatment with the water extract of Zizyphus vulgaris (WEZV) induced the levels of MT1 melatonin receptor expression and the levels of MT2 melatonin receptor expression was not affected. 3. The levels of MT1 as well as MT2 melatonin receptor expression were markedly up-regulated in the water extract of Fossilia ossis (WEFO) and the water extract of Ostreae caro (WEOC)-treated C6 cells. 4. The combination treatment with WEDL and WEZV induced not only the levels of MT1 melatonin receptor expression but also MT2 melatonin receptor expression, but the synergic effects of the combination treatment with WEFO and WEOC were not detected in C6 cells. Conclusion : The study provides important new insights into the possible mechanisms on the regulation of melatonin receptor synthesis by WEDL, WEZV, WEFO and WEOC.

• 동의신경정신과학회지
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• 제21권2호
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• pp.103-123
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• 2010

Objectives : This study was to investigate the effect of several herbal prescriptions such as Tianwangbuxindan qu zhusha, Tianwangbuxindan, Wendantang, Guipitang on the level of $MT_1$ and $MT_2$ melatonin receptors in C6 glial cells. Methods : For this study, we exposed of C6 cells to several herbal prescriptions resulted in non-cytotoxic in various dose as measured by MTT assay, trypan blue count, morphology change and DAPI stain. Results : Tianwangbuxindan qu zhush and Tianwangbuxindan induced the levels of $MT_1$ melatonin receptor expression in a dose-dependent manner without altering the level of $MT_2$ melatonin receptor expression. However, the treatment with Wendantang, Guipitang don't effect of $MT_1$ and $MT_2$ melatonin receptor expression. Conclusions : This results suggest that Tianwangbuxindan can be a promising the regulation of melatonin receptor synthesis, and further studies will be needed to clarify the mechanism.

• International Journal of Oral Biology
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• 제44권2호
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• pp.50-54
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• 2019

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced $[Ca^{2+}]_i$ increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

• 수면정신생리
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• 제22권1호
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• pp.5-10
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• 2015

The secretion of melatonin exhibits a circadian rhythm entrained with the sleep-wake cycle. An alteration of this secretory rhythm has been found in various psychiatric disorders. This review summarizes the regulation of melatonin and its relationship to the circadian rhythm, major depressive disorder, bipolar disorder, seasonal affective disorder, Alzheimer's disease and autism. The review also looks at the effect of melatonin and melatonin agonist on sleep and symptoms of depression, bipolar disorder and seasonal affective disorder. In Alzheimer's disease, the circadian rhythm alterations are associated with the change of melatonin levels and melatonin receptors. It has been reported that melatonin and melatonin synthetic enzyme levels decrease in autism spectrum disorder.

• The Korean Journal of Physiology and Pharmacology
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• 제12권2호
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• pp.37-41
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• 2008

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.

• 한국발생생물학회지:발생과생식
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• 제6권1호
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• pp.45-54
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• 2002

골든 햄스터의 생식활동은 광주기에 의해 조절된다. 그들의 생식능력은 여름에 왕성하고 겨울에는 퇴화한다. 송과선에서 분비되는 멜라토닌은 계절적 번식동물에서 생식활동을 중재한다. 멜라토닌 수용체가 최근에 사람을 포함하는 몇몇 동물에서 확인되었지만 골든 햄스터의 생식능력과 관련하여 알려진 바가 많지 않다. 역전사 PCR 방법을 사용하여 멜라토닌 수용체의 일부 유전자를 동정하였다(309 염기). 멜라토닌 수용체의 핵산 서열과 추론된 아미노산 서열을 보고된 다른 동물들과 비교하였다. 멜라토닌 수용체는 시상하부, 뇌하수체, 혈액, 지라에서 명백히 탐지되었다. 광주기가 정소 무게 및 생식 호르몬에 현저한 영향을 주었지만 멜라토닌 수용체의 발현에는 영향을 뚜렷하게 보이지 않았다. 이러한 결과는 생식을 조절하는 멜라토닌은 그 수용체의 수보다 수용체에 결합하는 친화도가 더 중요함을 시사한다.

• 한국산학기술학회논문지
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• 제6권2호
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• pp.183-188
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• 2005

포유동물에서는 두가지의 receptor가 보고되었다. 각 sample을 RNA extraction, RT-PCR, Realtime-PCR을 실시하여 melatonin 1A, 1B의 발현 양을 분석하였다. MT1A는 cerebellum에서는 3 hours에서 약 1/8배로 감소를 보이고 6 hours에서는 정상치 9 hours에서는 16배정도로 많은 양의 증가율 보였다. 나머지 hippocampus, thalamus, hypothalamus에서는 공통적으로 3 hours에서 많게는 10배에서, 적게는 대조군과 거의 비슷한 1.5배정도의 증가율을 보이고 있으며, 6 hours에서는 모두 감소하는 것을 알 수 있다. MT1B에서는 4 group 모두 3 hours, 6 hours에서 receptor의 양이 확연히 줄어들었다. 9 hours의 경우에는 4 group모두에서 적게는 8배, 많게는 거의 1000배 가까이의 발현 양의 차이가 나타났다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권10호
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• pp.1535-1541
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• 2018

Objective: In birds, three types of melatonin receptors (MTNR1A, MTNR1B, and MTNR1C) have been cloned. Previous researches have showed that three melatonin receptors played an essential role in reproduction and ovarian physiology. However, the association of polymorphisms of the three receptors with duck reproduction traits and egg quality traits is still unknown. In this test, we chose MTNR1A, MTNR1B, and MTNR1C as candidate genes to detect novel sequence polymorphism and analyze their association with egg production traits in Shaoxing duck, and detected their mRNA expression level in ovaries. Methods: In this study, a total of 785 duck blood samples were collected to investigate the association of melatonin receptor genes with egg production traits and egg quality traits using a direct sequencing method. And 6 ducks representing two groups (3 of each) according to the age at first eggs (at 128 days of age or after 150 days of age) were carefully selected for quantitative real-time polymerase chain reaction. Results: Seven novel polymorphisms (MTNR1A: g. 268C>T, MTNR1B: g. 41C>T, and g. 161T>C, MTNR1C: g. 10C>T, g. 24A>G, g. 108C>T, g. 363 T>C) were detected. The single nucleotide polymorphism (SNP) of MTNR1A (g. 268C>T) was significantly linked with the age at first egg (p<0.05). And a statistically significant association (p<0.05) was found between MTNR1C g.108 C>T and egg production traits: total egg numbers at 34 weeks old of age and age at first egg. In addition, the mRNA expression level of MTNR1A in ovary was significantly higher in late-mature group than in early-mature group, while MTNR1C showed a contrary tendency (p<0.05). Conclusion: These results suggest that identified SNPs in MTNR1A and MTNR1C may influence the age at first egg and could be considered as the candidate molecular marker for identify early maturely traits in duck selection and improvement.