• 생물정신의학
• /
• 제18권4호
• /
• pp.169-175
• /
• 2011

Stress, a risk factor of major depression induces cytokine mediated inflammation and decreased neurogenesis. In patients with major depression, significant increases of pro-inflammatory cytokines have been consistently reported. The pro-inflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal (HPA) axis to release glucocorticoids. In the brain, microglia and play a role of immune activation in response to stress. Increased pro-inflammatory cytokine play a role in restricting neurogenesis in the brain. Although neurogenesis may not be essential for the development of depression, it may be required for clinically effective antidepressant treatment. Hence, stimulation of neurogenesis is regarded as a promising strategy for new antidepressant targets. This review introduces changes in neurotransmitter, cytokine and neurogenesis in major depression and explores the possible relationship between pro-inflammatory cytokines and neurogenesis related to stress in major depression.

• Tuberculosis and Respiratory Diseases
• /
• 제52권5호
• /
• pp.529-538
• /
• 2002

배 경 : 급성 천식발작 치료의 근간을 이루는 전신성 스테이로드는 골다공증, 쿠싱증후군, 당뇨, 고혈압, 출혈성 경향 등의 합병증으로 초기에 흡입용 스테로이드 사용이 추천되고 있다. 흡입성 스테로이드에는 정량분무식 에어로졸(MDI)나 분말형 흡입제(DPI), 무화에어로솔(nebulized aerosol)를 사용해오고 있는데 소아나 노인, 호흡곤란이 아주 심한 성인 환자에서는 무화 에어로졸(nebulized aerosol)을 이용한 budesonide흡입이 효과적일 수 있다. 이에 급성 발작으로 내원한 성인 천식 환자에 nebulized budesonide를 적용했을 때의 임상적인 효과와 스테로이드 보존 효과, 스테로이드의 부작용 중 하나인 시상하부-뇌하수체-부신 축의 이상에 대한 영향을 알고자 하였다. 방 법 : 1. 2000년 6월부터 2001년 9월까지 입원한 기관지 천식, 천식을 동반한 만성 폐질환 환자를 선택하여 1군은 전신성 스테로이드와 nebulized budesonide 2mg을 사용한 군, 2군은 전신성 스테로이드와 budesonide turbuhaler를 사용한 군, 3군은 단지 전신성 스테로이드만을 사용한 군으로 나누고서 최대호기유속, 대기중 동맥혈가스검사, 폐기능검사, 증상지수(호흡곤란, 기침, 야간천식, 천명음), 스테로이드 총량, 입원기간를 기록하여 분석하였다. 2. 내원 10일전부터 어떤 종류의 스테로이드도 쓰지 않았던 환자를 선택하여 budesonide turbuhaler와 nebulized budesonide를 사용한 군으로 나누어 24시간 소변내 코타솔 수치를 측정하여 비교하였다. 결 과 : 1. 임상효과: 순수한 천식환자에서 증상 지수(호흡곤란, 천명음, 기침, 야간천식), 스테로이드 용량, 재원일수, 폐기능 소견, 최대호기유속, 동맥혈가스검사에서 세군간의 차이가 없었고, 천식을 동반한 만성 폐쇄성 폐질환환자를 대상으로 비교했을 때도 세균간의 차이는 없었다. 2. 시상하부-뇌하수체-부진 축의 효과 : nebulizer budesonide 사용군은 turbuhaler 사용군과 마찬가지로 부신축의 억제효과가 있으나 두 군간에 차이는 없었다.(p=0.288) 결 론 : 성인 천식환자에서 급성 발작시 budesonide 형태에 관련없이 전신성 스테로이드만이 치료에 도움을 줄 수 있다는 사실을 확인하였고, 치료 용량의 nebulizer 사용군에서 turbuhaler 사용군과 마찬가지로 시상하부-뇌하수체-부신 축에 대한 억제작용이 있었다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권1호
• /
• pp.113-125
• /
• 2023

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

• 대한수의학회지
• /
• 제44권2호
• /
• pp.207-215
• /
• 2004

It is well known that the hypothalamic-pituitary-adrenocortical (HPA) axis is under the negative feedback control of adrenal corticosteroids. Previous studies have suggested that glucocorticoids can regulate neuroendocrine cells in the paraventricular nucleus (PVN) by modulating catecholaminergic transmission, a major excitatory modulator of the HPA axis at the hypothalamic level. But, the effects of corticosteroids on the expression of adrenoceptor subtypes are not fully understood. In this work, we examined mRNA levels of six adrenoceptor subtypes (${\alpha}_{1A}$, ${\alpha}_{1B}$, ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\beta}_1$ and ${\beta}_2$) in the PVN of normal and adrenalectomized (ADX) rats. Total RNA ($2.5{\mu}g$) was extracted from PVN micropunches of brain slices ($500{\mu}m$) and analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The levels of corticotropin-releasing hormone (CRH) mRNA were increased in the ADX rats relative to normal rats, indicating that the PVN had been liberated from the negative feedback of corticosteroids. Among the six adrenoceptor subtypes examined, mRNA levels for ${\alpha}_{1B}$- and ${\beta}_1$-adrenoceptors were increased, but the level for ${\beta}_2$-adrenoceptors was decreased in the ADX rats. The mRNA levels for the other three subtypes and for the general and neuronal specific housekeeping genes, glyceroaldehyde-3-phosphate dehydrogenase (GAPDH) and N-enolase, respectively, were not changed in the ADX rats. In conclusion, the results indicate that adrenal steroids selectively regulate the gene expression of adrenoceptor subtypes in the PVN.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권5호
• /
• pp.393-403
• /
• 2013

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

• The Korean Journal of Physiology and Pharmacology
• /
• 제22권5호
• /
• pp.525-538
• /
• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

• 대한한의학회지
• /
• 제26권3호
• /
• pp.162-175
• /
• 2005

Backgrounds : Two stress pathways, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, regulate immune system responses through release of corticosteroids, norepinephrine and epinephrine. respectively. These neuromediators act on immune cells via specific receptors on their surface to modulate the production of key regulatory cytokines. Objectives : To evaluate the preventive effects of oriental medicine Hyeolbuchukyeo-tang (HC) on stress. Methods : Mice were divided into three groups: nounal group, control group under immobilization stress and HC group which received Hyeolbuchukyeo-tang (HC) under immobilization stress. following sacrifice, their splenocytes were isolated and splenocyte surface markers were determined. The brains were removed and mRNA determined. In vivo, we separated RNA Iron cultured macrophages (RAW264.7). Results : In our study, immune functions were decreased in stress due mainly to changes of various neuromediators, cytokines and macrophage activities, and the treatment of HC increased those expressions. Conclusions : In summary, the present study documents the anti-stress effects of HC through stress-immune regulation.

• 약학회지
• /
• 제60권1호
• /
• pp.8-14
• /
• 2016

Endotoxemia induces production of inflammatory mediators and acute phase proteins, leading to multiorgan injury and systemic inflammation. Hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoids (GCs) release modify endotoxemia-induced inflammatory responses. In the present study, we investigated whether pre-exposure of GCs influences endotoxin-induced production of inflammatory mediators in hepatocytes. Hepa1c1c-7 cells were pretreated with low concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS alone significantly enhanced production of IL-6 and CRP but reduced vascular endothelial growth factor (VEGF) compared to controls. Combination of corticosterone pretreatment and LPS significantly upregulated production of IL-6, IL-$1{\beta}$, and VEGF but downregulated CRP compared to those in LPS alone. These findings suggest that in low concentration of corticosterone-preexposed hepatocytes, endotoxemia may induce upregulation of IL-6, IL-$1{\beta}$, VEGF and but downregulation of CRP.

• 정신신체의학
• /
• 제19권2호
• /
• pp.109-114
• /
• 2011

연구목적: 시상하부-뇌하수체-부신 축의 이상은 다양한 정신과적 증상과 연관이 있으며, 우울 증상도 나타날 수 있다. 저자들은 뇌하수체 기능저하 및 이차성 부신기능저하와 연관된 두통, 무의욕, 무기력, 정신운동 저하, 식욕 저하, 불면 및 걱정 등의 우울 증상을 주소로 정신과에 입원한 71세 남자 환자에 대해 증례 보고하고자 한다. 환자는 정신과 입원 후 두통, 불면, 불안 및 소화기 증상은 호전되었으나, 무기력감은 지속되었다. 퇴원 후 고열 및 의식 혼탁으로 감염내과에 재입원을 하였으며, 부신기능 저하소견을 동반한 범뇌하수체기능저하증이 진단되었고, 코티졸 투여로 전반적인 증상이 호전되었다. 뇌하수체 기능저하에 따른 갑상선 기능저하, 부신기능저하, 성장호르몬 저하 등은 무기력, 피곤, 불면, 체중 감소, 식욕 저하 등의 여러 가지 비특이적 증상들을 나타내고, 임상에서 이러한 비특이적 우울 증상을 가진 환자의 경우, 내분비 질환에 대한 감별이 필요하다.

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