• 동의생리병리학회지
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• 제27권4호
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• pp.422-430
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• 2013

This experiment was designed to investigate the effects of So-Oochim-tang-Gagam-bang (SOCT-G) on oxidative stress and serotonin metabolism in P815 Mast Cells The effects of SOCT-G on activity of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging and Super Oxide Dismutase (SOD) in P815 mast cells were investigated. The effect of SOCT-G on content of serotonin in P815 mast cells was investigated. The effects of SOCT-G on expression of 5-hydroxytryptamine transporter (5-HTT), Tryptophan hydroxylase 1 (TPH-1) mRNA in P815 mast cells were investigated. The SOCT-G increased DPPH radical-scavenging activity in P815 mast cells. The SOCT-G increased SOD activity in P815 mast cells. The SOCT-G decreased the intracellular content of serotonin in P815 mast cells. The SOCT-G decreased 5-HTT and TPH-1 mRNA expression in P815 mast cells. This experiment shows that So-Ochm-Tang-Gagam-bang has a significant effect of oxidative stress that help prevent free radical damage. And So-Ochim-Tang-Gagam-bang decreased the intracellular content of serotonin and mRNA expression of 5-HTT and TPH-1. Therefore, further researches are suggested to reveal the anti-depressive effectiveness of So-Ochim-Tang-Gagam-bang.

• Journal of Acupuncture Research
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• 제18권1호
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• pp.21-28
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• 2001

Objective : The aim of this study was to investigate the effectiveness of stimulation of specific auricular acupuncture points on appetite suppression. Methods : The fasted rats were deprived of food and water for 48 hours. Stimulation of tho inner auricular region of the rat correspond to the human stomach acupuncture point was made for leptin, tryptophan hydroxylase (TPH) and c-fos expression in the brain of the fasted rats by immunohistochemistry. Results : The immunoteactivities of leptin in the periventricular nucleus of the auricular acupunctured group with fasted were significantly higher compared to those of the fasted group. The immunoreactivities of TPH in the median raphe neucleus and reticulotegmental neucleus pons of the auricular acupunctured group with fasted were significantty higher compared to those of the fasted group. And the immunoreactivities of c-fos in the dentate gyrus of the auricular acupunctured group with fasted were significantly lower compared to those from the fasted group. Conclusions : We conclude that the auricular acupuncture altered leptin and TPH-expression in the brain of the fasted rats. The results suggest that auricular acupuncture may inhibit food intake.

• Journal of Ginseng Research
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• 제44권4호
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• pp.644-654
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• 2020

Background: Posttraumatic stress disorder (PTSD), a mental disorder induced by traumatic stress and often accompanied by depression and/or anxiety, may involve an imbalance in the neurotransmitters associated with the fear response. Korean Red Ginseng (KRG) has long been used as a traditional medicine and is known to be involved in a variety of pharmacological activities. We used the open field test and forced swimming test to examine the effects of KRG on the depression-like response of rats after exposure to single prolonged stress (SPS), leading to activation of the serotonergic system. Methods: Male rats received KRG (30, 50, and 100 mg/kg, intraperitoneal injection) once daily for 14 days after exposure to SPS. Results: Daily KRG administration significantly improved depression-like behaviors in the forced swimming test, increased the number of lines crossed and time spent in the central zone in the open field test, and decreased freezing behavior in contextual and cued fear conditioning. KRG treatment attenuated SPS-induced decreases in serotonin (5-HT) tissue concentrations in the hippocampus and medial prefrontal cortex. The increased 5-HT concentration during KRG treatment may be partially attributable to the 5-hydroxyindoleacetic acid/5-HT ratio in the hippocampus of rats with PTSD. These effects may be caused by the activation of hippocampal genes encoding tryptophan hydroxylase-1 and 2 mRNA levels. Conclusion: Our findings suggest that KRG has an antidepressant effect in rats subjected to SPS and may represent an effective use of traditional medicine for the treatment of PTSD.

• Animal cells and systems
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• 제16권3호
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• pp.190-197
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• 2012

Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.

• 한방재활의학과학회지
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• 제29권2호
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• pp.91-99
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• 2019

Objectives The loss of maternal care during early postnatal period may increase development of mood-related disorders, such as depression, anxiety, and personality disorders. In this study, the effect of acupuncture on depression in relation with cell proliferation in the hippocampal gyrus dentatus was investigated using maternal-separated rat pups. Methods On the postnatal 14th day, rat pups from six dams were grouped into following groups: maternal care group, maternal separation group, maternal separation and non-acupoint-acupunctured group, maternal separation and Zusanli-acupunctured group, and maternal separation and fluoxetine-treated group. Acupuncture was performed from postnatal 28th day to postnatal 37th day. The rat pups that belong in the maternal separation and fluoxetine-treated group were injected subcutaneously with 5 mg/kg fluoxetine hydrochloride once a day for the same period of time. To evaluate activity of the rat pups, open field test was performed. Immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe and for 5-bromo-2'-deoxyuridine (BrdU) in the hippocampal gyrus dentatus was conducted. Results The present results reveal that the activity was decreased by maternal separation. In contrast, acupuncture at Zusanli overcame maternal separation-induced hypoactivity. Maternal separation suppressed TPH expression and 5-HT synthesis in the dorsal raphe and decreased cell proliferation in the hippocampal gyrus dentatus of rat pups. In contrast, acupuncture at Zusanli alleviated maternal separation-induced decrease of 5-HT synthesisand TPH expression. Conclusions The present results demonstrate that acupuncture at Zusanli ameliorated depressive state through increasing cell proliferation and enhancing 5-HT synthesis.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.449-457
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• 2021

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin's wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride co-transporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

• Journal of Ginseng Research
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• 제46권6호
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• pp.819-829
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• 2022

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABA_A antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABA_A receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

• 생물정신의학
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• 제15권1호
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• pp.14-22
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• 2008

우울 장애는 유전적 요인과 함께 환경적 요인이 복합적으로 작용하는 정신 장애이다. 본 연구에서는 세로토닌 체계와 연관된 유전적 요인과 생활사건과 같은 환경적 요인이 초기 성인기 우울 장애 발현에 미치는 영향을 조사함으로써 우울 장애의 원인론에 있어 유전자${\times}$환경 상호작용을 설명할 수 있는 자료를 제시하고자 하였다. 534명의 대학 신입생을 종적으로 추적 조사하여 생활사건 빈도와 중요도, 우울 척도와 불안 척도를 조사하였으며 전화 면담을 통해 DSM-IV 우울 장애 여부를 확인하였다. 최종적으로 150명이 연구에 포함되었으며 이전 연구로 확인된 TPH1 유전형과 함께 보관되어 있던 대상군의 DNA를 이용하여 SNaPshot$^{TM}$ 방식으로 TPH2, 5HTR2A 유전자를 추가 분석하였다. 유전자 정보와 생활사건 특성이 우울 증상에 미치는 영향을 확인하기 위해 로지스틱 회귀 분석과 상관 분석, 카이 자승 분석을 사용하였다. TPH1 유전형 중 C 대립 유전자가 존재하지 않는 집단과 달리 C 대립 유전자가 존재하는 집단에서는 생활사건 빈도가 우울 장애 유발에 유의한 영향을 미쳤다. 이러한 영향은 다른 대립 유전자나 유전형을 보이는 집단에서는 관찰되지 않았다. 본 연구의 결과는 TPH1 유전형은 생활사건 이후 우울 장애 발생의 유의미한 예측 요인임을 시사한다. 이는 우울 장애의 유전${\times}$환경 상호작용에 TPH1 유전자가 작용하고 있음을 제시한다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권12호
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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.

• 대한약침학회지
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• 제3권1호
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• pp.35-51
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• 2000

The purpose of this study is to prove the analgesic effects of apitoxin and its mechanism via jaw-opening reflex(JOR) and measuring expression of mRNA in Phospholipase and Tryptophan hydroxylase(TPH) using RT-PCR. The experiments were carried out on Sprague-Dawley rats(300-400g) and mastocytoma(P-185 HTR) for JOR and RT-PCR, respectively. Rats anesthetized with thiopental sodium (80mg/kg) were used in the Tooth Pulp stimulation induced JOR. The amplitude of a digastric electromyogram (dEMG) was recorded during the stimulation at an intensity of 1.5 times the threshold for JOR. Apitoxin used in this experiment was diluted with normal saline by 1:1000. Apitoxin was injected intravenously into the test group while normal saline to the control group. However, it was injected directly into the cell of mastocytoma. We referred to base sequence registered in Genbank in designing primers for RT-PCR. The results were as follows; (1)Compared with control group, analgesic effect started to show right after Sprague-Dawely rats were treated with apitoxin($71.50{\pm}8.08$) and lasted for 50 minutes. (2)As a result of the experiment of RT-PCR, we witnessed significant changes in the degree of expression of phospholipase or rate-limiting enzyme of biosynthesis of prostaglandins with $10{\mu}g/ml$ apitoxin.($31.74{\pm}18.98%$, P<0.05) (3)As a result of the experiment of RT-PCR, we witnessed significant changes in the degree of expression of TPH or rate-limiting enzyme in biosynthesis of serotonin with $10{\mu}g/ml$ apitoxin.($131.37{\pm}16.87%$, P<0.05). These results suggest that $10{\mu}g/ml$ apitoxin have the most analgesic effects. This study showed that apitoxin has analgesic effects and held good for 50 minutes. The injection of apitoxin has brought out changes in the degree of expression of phospholipase and TPH. These results strongly suggest that analgesic mechanism by apitoxin is closely related to prostaglandins and serotonin.