• 대한의생명과학회지
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• 제15권3호
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• pp.249-255
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• 2009

All living things have been developed efficient strategies to cope with external and internal environmental changes via a process termed 'homeostasis'. However, chronic prenatal maternal stress may significantly contributes to pregnancy complications by disturbing hypothalamic-pituitary-adrenal (HPA) axis and the automatic nervous system (ANS), and results in unfavorable development of the fetus. Dysregulation of these two major stress response systems lead to the increased secretion of the glucocorticoids (GCs) which are known to be essential for normal development and the maturation of the central nervous system. As Hox genes are master key regulators of the embryonic morphogenesis and cell differentiation, we aimed to determine the effects of dexamethasone, a potent synthetic glucocorticoid, on gene expression in mesenchymal stem cell C3H10T1/2. Analysis of 39 Hox genes based on reverse transcription PCR (RT-PCR) method revealed that the expression patterns of Hox genes were overall upregulated by long dexametasone treatment. These results indicate that maternal stress may have a deleterious effect on early developing embryo through the stress hormone, glucocorticoid.

• Journal of Microbiology and Biotechnology
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• 제22권5호
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• pp.708-720
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• 2012

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stress-induced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced open-arm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

• 대한한방부인과학회지
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• 제26권4호
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• pp.30-47
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• 2013

목 적: 본 연구는 만성 스트레스로 인한 갱년기 우울증 모델에서 사물탕가향부자(SGH)의 항우울 효과를 검증하여 실험적 유의성을 확인하고자 시행되었다. 방 법: 난소적출 흰쥐에 4주간 만성 스트레스를 가하고 SGH(100 and 400 mg/kg/day)를 투여한 후 행동검사인 sucrose intake test(SIT), elevated plus maze(EPM), forced swimming test(FST) 및 Morris water maze test(MWMT) 등을 통한 우울행동 변화와 혈청 corticosterone(CORT), IL-$1{\beta}$ 및 IL-4 등의 변화를 측정하였고, 또한 뇌 내 hippocampus와 hypothalamus에서 5-HT의 변화를 측정하였다. 결 과: 1. SIT에서 SGH 400 mg/kg/day 투여군은 대조군에 비해서 자당 섭취가 유의하게 증가하였다(p<0.05). 2. EPM에서 SGH 400 mg/kg/day 투여군은 대조군에 비해서 open arms에 머무는 시간이 유의하게 증가하였고(p<0.01), open arms와 closed arms를 교차하는 횟수도 대조군에 비해서 유의하게 증가하였다(p<0.05). 3. FST에서 SGH 100 mg/kg/day, 400 mg/kg/day 투여군 모두 대조군에 비해서 immobility시간이 유의하게 줄어들었다(SGH 100 p<0.05, SGH 400 p<0.01). 4. MWMT에서 SGH 100 mg/kg/day, 400 mg/kg/day 투여군은 모두 대조군에 비해서 실험 4일째에서 acquisition trials 수행 시간이 유의하게 단축되었고(p<0.05), SGH 400 mg/kg/day 투여군은 대조군에 비해서 retention trials 수행 시간이 유의하게 증가하였다(p<0.05). 5. CORT와 IL-4 측정에서 대조군과 SGH 투여군 모두 유의한 변화가 없었고, IL-$1{\beta}$ 측정에서 대조군에서는 유의하게 증가하였지만 SGH 투여군에서는 대조군에 비해서 유의한 변화가 없었다. 6. Hippocampus에서의 5-HT 측정에서 SGH 400 mg/kg/day 투여군은 대조군에 비해서 유의하게 증가하였다(p<0.05). Hypothalamus에서의 5-HT수준은 SGH 투여군 모두 대조군에 비해서 유의하게 증가하였다(SGH 100 p<0.05, SGH 400 p<0.01). 결 론: 이상의 결과로 SGH는 만성 스트레스를 가한 난소적출 흰쥐에서 항우울 효과가 있음을 알 수 있었고, HPA axis, immune system 보다 5-HT system에 작용하는 것으로 사료된다.

• Journal of Ginseng Research
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• 제32권1호
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• pp.8-14
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• 2008

스트레스 반응은 위급 상황에서만 활성화 되는 것이 아니라 우리 주변을 둘러싼 모든 사회적, 물리적 환경에 의해 끊임없이 기인된다. 예를 들어 소음, 강한 빛과 열, 주거의 공간 등과 같은 물리적 환경과 타인과의 관계, 부당한 대우, 규칙, 형식과 같은 사회적 관계 이 그것이다. 고려 인삼은 항스트레스 작용을 한다고 알려져 있으나 현재까지 대부분의 연구는 인삼 엑기스 또는 총 사포닌을 투여 시 나타나는 물리화학적인 척도 (수영 시간, 뜨거움에 대한 반응, 포도당 및호르몬 수준 등)를 측정하였으며 뇌에서 ginsenoside의 기능연구는 매우 미흡한 수준이다. 특히 신호전달, 전사체 (transcriptome),proteomics, system biology와 같은 분자생물학적인 방법을 이용한 기전 연구는 전혀 수행된 바 없다. 따라서 인삼의 항 스트레스 반응 기전을 이해하기 위해서는 인삼투여 후 뇌에서 나타나는 분자적 변화에 대한 연구가 앞으로 요구된다. 또한 microarray 등의 분자생물학적 기법을 이용하여 인삼 투여에 의해 반응하는 유전자를 발굴함으로써 이러한 인자들이 인삼 효능 시험 등에 지표로 응용될 수 있을것이다.

• Journal of Korean Biological Nursing Science
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• 제18권1호
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• pp.36-42
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• 2016

Purpose: Stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis and induces the release of glucocorticoids. Saccharin is 300 times sweeter than sucrose, but does not increase blood insulin levels. Thus, this study was designed to evaluate the effect of saccharin intake in restraint-induced stress response reduction in rats. Methods: Adult male Sprague-Dawley (SD) rats had stress induced by restraint for 2 hours/day for 1 week. Saccharin was provided in sufficient amounts to allow them to intake it voluntarily at 0.1% diluted in water. The Y-maze test and forced swim test (FST) were performed to evaluate cognitive function and the depressive behavior of the rats. The protein expression of the glucocorticoid receptor (GR) in hippocampal cornu ammonis (CA) 1 was investigated by using immunohistochemistry. Results: It was found that, the percentage of alternation in the Y-maze test was significantly (p<.01) higher in the Stress + saccharin group than in the Stress group. Immobility time in the FST was significantly (p<.01) lower in the Stress + saccharin group than in the Stress group. Also, the positive cells of GR in hippocampus CA1 were significantly (p<.05) lower in the Stress + saccharin group than in the Stress group. Conclusion: This study showed that there was an effect of saccharin intake in restraint-induced stress response reduction in rats.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.191-200
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• 2014

We investigated the anxiolytic-like activity of ${\alpha}$-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.213-222
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• 2014

Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitaryadrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.

• Journal of Oral Medicine and Pain
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• 제32권2호
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• pp.201-210
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• 2007

많은 질병들과 기존에 존재하는 신체적인 질병들은 스트레스로 인해 발병되거나 크고 작은 스트레스의 영향으로 악화된다. 스트레스의 연구에 호르몬을 사용하는 기본은 신체의 대부분 시스템이 스트레스를 받는 동안 변화를 보인다는 것과 이러한 변화에 호르몬이 스트레스와 확실하게 연관되어 있다는 것을 관찰하는 것이다. 개념적으로 스트레스에 있어서 교감신경계와 시상하부-뇌하수체-부신축의 활성화가 중심적인 역할을 한다는 것이 호르몬의 변화를 측정해야 할 충분한 근거를 제공한다. 에피네프린과 노르에피네프린과 같은 카테콜라민, 코티졸, 테스토스테론 그리고 성장호르몬 등은 스트레스에 예민한 반응을 보인다. 한편 스트레스 연구를 위한 타액표본은 혈액이나 요의 표본과는 달리 스트레스를 주지 않고도 표본을 얻을 수 있으며 신체적인 구속이나 윤리적인 문제 등을 염려하지 않고도 채취가 가능하다는 장점이 있다. 타액내의 호르몬의 수치는 혈액내의 호르몬 수치를 잘 반영하므로 스트레스와 관련된 구강안면통증의 연구에 있어서 타액내의 스트레스 호르몬에 활용도는 매우 높으리라고 사료된다.

• The Korean Journal of Pain
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• 제18권1호
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• pp.15-18
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• 2005

Background: Epidural steroid injections (ESI) have been used widely for the treatment of back and radiating extremity pain. Although its effects on the metabolic and endocrine system have been studied, the effects following repeated injections remain to be determined. We studied the effects of three repeated caudal epidural injections of low dose triamcinolone. Methods: the subject were 10 elderly women with spinal stenosis. Caudal epidural injections were performed biweekly. Triamcinolone (20 mg), mixed with 15 ml of 0.25% lidocaine, was used as the ESI injectate. The procedures were performed with the patient in the prone position. Blood sampling was performed just before the first injection, and used as the baseline, and then just before each injection on the same day of the 2nd and 4th weeks, with the last samples taken 2 weeks after the third injection. Results: The blood glucose concentrations showed no significant changes. The blood cortisol and ACTH concentrations were significantly decreased after the first injection, but there were no further decreases after each of the subsequent injections. The cortisol concentrations were maintained within the normal range. Conclusion: Caudal epidural injections, with low dose triamcinolone, suppressed the hypothalamus-pituitary-adrenal (HPA) axis, but no further suppression followed the subsequent repeated injections. Three consecutive caudal injections at 2 week intervals seems to be a safe procedure.

• 대한불안의학회지
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• 제4권1호
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• pp.19-27
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• 2008

Objective : This study was conducted to evaluate the changes in the levels of neurotransmitters and cortisol in patients with chronic posttraumatic stress disorder (PTSD) and to evaluate their correlation with symptoms after long-term pharmacological treatment. Methods : Twenty-eight Vietnam veterans with chronic PTSD and 34 non-PTSD patients were consecutively recruited. The Combat Exposure Scale (CES), Mississippi Scale for Combat-Related Posttraumatic Stress Disorder (M-PTSD), Clinician Administered PTSD Scale (CAPS), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Scale (HAS) were used to evaluate symptom severity. High performance liquid chromatography (HPLC) was used to measure the plasma levels of epinephrine, norepinephrine, and dopamine, and a radioimmunoassay (RIA) was performed to evaluate the plasma level of cortisol. Results : Plasma cortisol was significantly lower in PTSD patients than in control subjects, while there was no significant difference in plasma epinephrine, norepinephrine and dopamine between the two groups. The scores of M-PTSD, CAPS, HAMD and HAMA were signigicantly higher in PTSD patients than control group. Conclusion : After long-term treatment, the levels of neurotransmitters in PTSD patients returned to within the normal range, and the patients' symptoms showed some improvement. However, the core symptoms of PTSD continued to appear intermittently, and they are thought to be associated with hormonal systems, such as the HPA axis. It is also suggested that PTSD should be considered to be a complex disorder associated with multiple systems and that combinations of the effective medications for each system should be used to treat patients with PTSD.