Stress-induced Neuroimmuno Alterations in the Rat

Hyun-ju Lee,Kyung Soo Kim,Insop Shim 대한스트레스학회 2010 스트레스硏究 Vol.18 No.2

스트레스는 서로 상호작용을 하는 중추신경계, 내분비계 그리고 면역계에 영향을 준다. 구금스트레스는 시상하부-뇌하수체-부신피질로 이어지는 축(Hypothalamic-pituitary-adrenal axis, HPA-axis)을 활성화시키고 전 염증성, 항 염증성 사이토카인 발현에도 변화를 초래한다. 청반(locus coeruleus)은 스트레스에 반응하는 뇌간의 부분으로 시상하부의 뇌실곁핵에 투사하므로 HPA-축의 활성화에 영향을 끼친다. 본 논문에서는 구금스트레스로 인한 HPA-축 호르몬과 항염증성 사이토카인인 인터루킨-4의 발현 변화를 관찰하고 HPA-축의 최종 호르몬인 코르티코스테론을 주입하였을 때 인터루킨-4의변화를 관찰함으로써, 스트레스 하에서 HPA-축과 인터루킨-4의 상호작용에 대해 밝히고자 하였다. 또한, 면역조직화학법을 통해 청반에서 인터루킨-4를 발현하는 신경세포를 동정하고자 하였다. 실험결과 급성 구속 스트레스에 의해 증가되었던 HPA-축 호르몬들은 반복 구속스트레스를 받았을 때 유의하게 감소하여 지속적인 스트레스에 대한 적응 양상을 나타내었다. 또한, 급성 또는 반복 스트레스를 받았을 때와 코르티코스테론을 반복적으로 주입하였을 때 청반에서의 인터루킨-4 발현이 감소함을 보였다. 이러한 결과는 스트레스 상황에서 활성화 된 HPA-axis가 청반과 상호작용을 하여 인터루킨-4 발현을 감소시킴을 시사한다. Severe stress such as immobilization (IMO) affects the central nervous system, the endocrine system and the immune system that interact each other. IMO-induced responses are activation of hypothalamic-pituitary-adrenal (HPA) axis and production of inflammatory cytokine. The locus coeruleus (LC), which is known to play a role in modulating stress response, innervates the paraventricular neucleus (PVN) of the hypothalamus thereby activating HPA-axis. In this study, IMO-induced alterations of HPA-axis hormones and interleukin-4 (IL-4) were investigated. The final hormone of HPA-axis, corticosterone (CORT) was injected to clarify the interaction of the HPA-axis and IL-4 in the stress response. Single exposure of stress resulted in an increase of corticotrophin-releasing factor expression in the PVN, adrenocorticotropin hormone and CORT levels in the serum. Increased expressions of HPA-axis hormones in the acute stressed group were decreased in repeated stressed group. IL-4 level in the LC of the brain was decreased in both stressed group and repeated CORT injected group. These results suggest the possibility of stress-induced interplay of HPA-axis and IL-4 in the LC.

Stress-induced Neuroimmuno Alterations in the Rat

이현주,김경수,심인섭 대한스트레스학회 2010 스트레스硏究 Vol.18 No.2

Severe stress such as immobilization (IMO) affects the central nervous system, the endocrine system and the immune system that interact each other. IMO-induced responses are activation of hypothalamic-pituitary-adrenal (HPA) axis and production of inflammatory cytokine. The locus coeruleus (LC), which is known to play a role in modulating stress response, innervates the paraventricular neucleus (PVN) of the hypothalamus thereby activating HPA-axis. In this study, IMO-induced alterations of HPA-axis hormones and interleukin-4 (IL-4) were investigated. The final hormone of HPA-axis, corticosterone (CORT) was injected to clarify the interaction of the HPA-axis and IL-4 in the stress response. Single exposure of stress resulted in an increase of corticotrophin-releasing factor expression in the PVN, adrenocorticotropin hormone and CORT levels in the serum. Increased expressions of HPA-axis hormones in the acute stressed group were decreased in repeated stressed group. IL-4 level in the LC of the brain was decreased in both stressed group and repeated CORT injected group. These results suggest the possibility of stress-induced interplay of HPA-axis and IL-4 in the LC. (Korean J Str Res 2010;18:81∼86)

스트레스, 우울증과 HPA 축의 관련성

우영섭,박원명 대한우울조울병학회 2014 우울조울병 Vol.12 No.1

Major depression is highly prevalent mental illness and one of the leading causes of premature death and disability. Despite the high prevalence and disabilities, knowledge about pathophysiology of depression is still rudimentary. In this review, we summarize the current state of knowledge of the mechanism of depression, especially concentrate on the recent advances in the role of stress system. Considering its role at the interface between stress and brain functioning, it is perhaps not surprising that the Hypothalamic-Pituitary-Adrenal axis (HPA axis) has been found abnormal in depression. HPA axis activity is governed by the secretion of corticotropin-Releasing Hormone (CRH) and vasopressin (AVP) from the hypothalamus, which activate the secretion of adrenocorticotrophic hormone (ACTH) from the pituitary, which subsequently stimulates the secretion of the glucocorticoids from the adrenal cortex. Glucocorticoids then interact with their receptors in multiple target tissues including the HPA axis. We will present data supporting the hypothesis that HPA axis hyperactivity and abnormality in its components is not a simple consequence or an epiphenomenon of depression, but on the contrary that it is a risk factor predisposing to the development of depression.

한국인 사회적 음주자에서 매운맛 선호도와 스트레스에 대한 HPA축 반응의 연관성

박지훈(Ji-Hun Park),김성곤(Sung-Gon Kim),김지훈(Ji-Hoon Kim),정우영(Woo-Young Jung),이진성(Jin-Seong Lee),변원탄(Won-Tan Byun) 대한생물치료정신의학회 2014 생물치료정신의학 Vol.20 No.2

Objectives:Some reports suggest that if individuals prefer spicy foods, they may be more vulnerable to stress; thus, their HPA axis reactivity to stress may be abnormal. We investigated the relationship between HPA axis reactivity to stress and spicy food preference in Korean social drinkers. Methods:The subjects were 40 healthy social adult drinkers >18 years. They were exposed to stress as cold pressor test and mathematical calculations. Salivary cortisol level was measured before and after the stress. In addition, spicy food preference was measured using a food preference scale. The subjects were divided into two groups of those who preferred spicy foods(SP, n=20) and those who less preferred spicy foods(LP, n=20). Results:Repeated measures ANOVA on salivary cortisol concentration revealed a significant group by block interaction(p=0.036). Basal and salivary cortisol levels immediately after stress were significantly higher in SP subjects than those in LP subjects(respectively p=0.009, p=0.011). The salivary cortisol level at 80 min after the stress decreased significantly compared to the basal salivary cortisol level in SP subjects(p=0.004). Salivary cortisol level 20 min after the stress increased significantly compared to the basal salivary cortisol level in LP subjects(p=0.031). Conclusion:HPA axis reactivity to stress in SP subjects was more sensitive than that in LP subjects. These results suggest that HPA axis reactivity in those who prefer spicy foods may be vulnerable to stress.

Modulation of corticosterone and changes of signal molecules in the HPA axis after cold water swimming stress

Feng Jing-Hui,심수민,박정석,홍재승,서홍원 한국통합생물학회 2021 Animal cells and systems Vol.25 No.1

In the present study, we examined the effect of cold-water swimming stress (CWSS) on plasma corticosterone levels. Mice were exposed to stress in 4°C for 3 mins. Plasma corticosterone (CORT) level was measured at 0, 15, and 30 min after stress stimulation. The plasma CORT level was gradually increased up to 30 min. Then we further examined the changes of several signaling molecules expression levels, such as p-ERK, p-JNK, p-P38, p-AMPKα1, p-AMPKα2, and p-mTOR, in the HPA axis. We observed that those signaling molecules were altered after stress in the HPA axis. p-ERK, p-JNK, p-P38, and p-mTOR proteins expression were reduced by CWSS in the HPA axis. However, the phosphorylation of AMPKα1 and AMPKα2 were activated after CWSS in the HPA axis. Our results suggest that the upregulation of plasma CORT level induced by CWSS may be modulated by the those signaling molecules.

시상하부-뇌하수체-부신 축과 우울증 : 임상적 의미

서정석 대한우울조울병학회 2014 우울조울병 Vol.12 No.1

Physiologically, hypothalamus-pituitary-adrenal axis (HPA) has effects on neuronal survival, neurogenesis, change of size, and the acquisition of new memories and the emotional appraisal of events in the brain. Although over-activity of HPA in the patients with major depressive disorder (MDD) has been reported at the rate of 20-40%, the relationship between HPA and depression has been controversial. Some evidences supported that a restoration of hyperactive HPA is the mediator for the clinical action of antidepressant drug. That is whether the hypercortisolism is a trait marker or state marker of MDD. Also clinical usefulness of dexamethasone suppression test (DST) is not clear to diagnose MDD and predict the recurrence of MDD. However, consecutive two or more DST rather than once would be useful to predict the response and remission of MDD to antideressant treatment. Furthermore, there is a possibility that HPA receptor, especially glucocorticoid receptor agonist/antagonist, is taken as a new target of pharmacological treatment for depressive disorder. These findings implicated that there might be sub-populations within patients with MDD who respond positively to DST.

지골피(地骨皮)와 치자(梔子) 합제(合劑)가 강제수영부하실험에서 HPA-Axis와 Catecholamine system에 미치는 영향

오정진,이태희,Oh, Jeong-Jin,Lee, Tae-Hee 대한한의학방제학회 2012 大韓韓醫學方劑學會誌 Vol.20 No.1

Objectives : In this study the antidepressant effects of mixture of Lycii Radicis Cortex and Gardeniae Fructus on the change of HPA-Axis and Catecholamine system was investigated Methods : The forced swimming test was performed. The expression of CRF, c-Fos in the PVN, and TH in the VTA and LC were measured with immunohistochemical method. And the experimental groups were divided into the Extraction after Mix group(A) and Mix after Extraction group(B). The effects of both group were compared. Results : The duration of immobility in the FST was decreased significantly in three groups except B100(P<0.01). B100 was shown the significant increase(P<0.05). The expression of CRF in PVN was decreased significantly in all group(P<0.05~P<0.01). The expression of c-Fos in PVN was decreased in A100, A400 and was increased significantly in B100, B400(P<0.05). The expression of TH in VTA and LC were decreased significantly in all group(P<0.001). Conclusions : Effects of Extraction after Mix group(A) and Mix after Extraction group(B) on the HPA-Axis system and Catecholamine system were validated.

기관지 천식 환자에서 단기간의 부신피질호르몬제 투여가 뇌하수체 및 부신피질 기능에 미치는 영향

김옥란(Ok Lan Kim),서승천(Seung Cheon Seo),허성호(Sung Ho Hue),최병휘(Byung Hue Choi),배혜상(Hae Sang Bae),성천모(Cheon Mo Seong),이재용(Jae Yong Lee),최민석(Min Seok Choi),이원돈(Won Don Lee) 대한내과학회 1989 대한내과학회지 Vol.36 No.1

N/A Short-term, high dose corticosteroid therapy is often required for control of acute asthma episodes. To evaluate possible Hypothalamic-Pituitary-Adrenal (HPA)-axis suppression and recovery after such therapy, we studied 7 patients with adult acute asthma before and at 1, 3 and 7 days after completion of a 12 day course of corticosteroid. Corticosteroid was administered as a loading dose (methylprednisolone which was equivalent to 4 mg of hydrocortisone/kg body weight) and maintenance dose (equivalent to 3mg of hydrrcortisone/kg body weight/6 hours) for 3 days, followed by prednisolone (usual start dose was prednisolone 60 mg as a single daily morning dose). The dose was then reduced in half every 3 days. The function and reserve of the HPA-axis were evaluated with basal plasma cortisol, ACTH and short corticotropin stimulation tests. The results obtained were as follows: 1. Baseline plasma cortisol, ACTH, and cortisol responses to corticotropin before corticosteroid treatment were 10.3±5.6 ㎍/dl, 25.4±8.4 /㎍/ml, and 17.7±6.2 ㎍/dl, respectively. 2. One day after corticosteroid therapy, plasma cortisol and ACTH levels (3.9±2.4 ㎍/dl, 9.2±9.0 pg/ml) were significantly reduced compared to pretreatment levels (p<0.01. p<0.01), but the cortisol responses to corticotropin were preserved. 3. Three days after concluding the corticosteroid therapy, plasma cortisol and ACTH levels had returned to 68.9% and 71.7% of the pretreatment levels respectively, and were restored to near pretreatment baseline levels 7 days after treatment. These data suggest that a brief course of high dose corticosteroid treatment may limit the adrenal component of HPA responses for up to 7 days and patients may be at risk if they encounter major surgery or infection during this time.

지골피(地骨皮)가 강제수영부하실험에서 HPA-Axis System에 미치는 영향

구범모,이태희,Koo, Beom-Mo,Lee, Tae-Hee 대한한의학방제학회 2010 大韓韓醫學方劑學會誌 Vol.18 No.2

In order to investigate the antidepressant effects of Lycii Radicis Cortex on the change of HPA-Axis system, the forced swimming test was performed. The expressions of CRF and c-Fos in the PVN were measured with immunohistochemical method and the concentration of ACTH in Serum was evaluated with ELISA method. And the results obtained were as follows. Results : 1. The duration of immobility in the forced swimming test was significantly decreased in the LRC100 group and the LRC400 group(P<0.001). 2. The expressions of CRF and c-Fos were significantly reduced in the LRC100 group and the LRC400 group(P<0.001). And the concentration of ACTH in Serum were significantly reduced in the LRC 100 group(P<0.05). According to the results above mentioned, it can be considered that Lycii Radicis Cortex has antidepressant effects.

일회성 유산소운동 후 다량의 알코올섭취가 HPA축과 체온의 주기리듬에 미치는 영향

고성경(Ko, Seong-Kyeong),류호상(Yoo, Ho-Sang),권영우(Kwon, Yeung-Woo),김한철(Kim, Han-Chu),권광선(Kwon, Kwang-Sun),김진형(Kim, Jin-Heung) 한국체육과학회 2014 한국체육과학회지 Vol.23 No.1

The aim of this study was to investigate the effects of an acute large amount of alcohol ingestion(17% distilled alcohol, 9ml/㎏ per 1㎏ body weight) after aerobic exercise on circadian rhythm of HPA axis(ACTH, cortisol), body temperature. Alcohol degradation ability also measured. Twelve male (average age 33.5years, weight 73.1㎏) took part in this study and performed 3 trials (alcohol ingestion after exercise, alcohol ingestion. placebo ingestion) in a randomized, cross-over design at intervals of 1 weeks. They drank dry white wine(mixed with orange) at 18:00hours during 45 minutes. Placebo treatment ingested identical amount of fluid not contained alcohol. Resting blood sample extracted at 24:00hours and 0700hours(following day) for measuring circadian variation. Extra blood also extracted during 30, 120min after alcohol ingestion for alcohol degradation ability. Exercise treatment group performed running at 70%HRmax during 30 minutes by treadmill. Blood cortisol concentration were significantly high by only alcohol ingestion as compared to exercise+alcohol ingestion and placebo ingestion treatment during 07:00 and 24:00hours. The present findings suggest that large alcohol ingestion may deteriorate circadian rhythm and exercise before alcohol ingestion alleviate thus alcohol ingestion related circadian rhythm disorder.