Effect of acute or subchronic stress on T cell response in peripheral blood: Regulatory role of vitamin D

The immune response, orchestrated by helper (Th1, Th2, and Th17) and regulatory (Treg) T cells, is modulated by stress and Vitamin D (Vit-D). Although the immunomodulatory functions of both are known, their specific roles on Th cells have not been fully clarified, yet. On this background, we aimed to investigate the effect of acute or subchronic stress on the distribution of peripheral T lymphocytes, as well as the immunomodulatory role of Vit-D. Young adult male, Swiss-albino mice (30–40g) were allocated to the control, acute stress (AS), subchronic stress (ChS), control+Vit-D, AS+Vit-D, and ChS+Vit-D groups (n=11/group). The combined cold (2-h at 4°C)-immobilization (2-h in a restrainer) stress protocol was employed as one day in AS groups and five consecutive days in ChS groups. Vit-D (2?g/kg ip) was applied every other day, until the end of the protocol. Serum cortisol, Vit-D and cytokine levels (IL-4, IFN-?, and IL-17A) were measured, and lymphocytes from blood samples were subtyped by flow-cytometry. Stress exposure caused differential Th and Treg responses, acute stress shifting the response to Th1, and subchronic stress shifting the response to Th2. Th17 and Treg cells were lower in subchronic stress exposed mice. These changes became comparable to control values in Vit-D treated groups. The T cell response, crucial for immune system function, differs on the basis of stress exposure as such the Vit-D treatment. The tolerogenic profile created by Vit-D should be considered for management of stress-related diseases. Our results may help to provide a better understanding of disease pathogenesis.

Effects of repeated immobilization stress on hypothalamic-pituitary- ovarian axis in female rats / 中国应用生理学杂志

To explore the effects of repeated immobilization stress on hypothalamic-pituitary-ovarian axis in female rats. Methods: Forty female SD rats were randomly divided into two groups: control group (n=20) and experimental group (n=20). One group was fed normally, the other group was subjected to incremental load restraint stress. Brake stress once a day in the retainer (starting at 9: 00 a.m.), braking for 2 hours on the first day, increasing load by 0.5 hours a day for two weeks. Body weight, estrous cycle, sex hormone, organ coefficient, pathology and expression of related genes were detected to explore the harm of hypothalamic-pituitary-ovarian axis. Repeated immobilization stress caused weight loss, prolonged estrous cycle, and changed the organ coefficient and morphology of ovaries and uterus. QPCR technique was used to detect the related genes. It was found that the expressions of gonadotropin releasing hormone, pituitary gonadotropin releasing hormone receptor, follicle stimulating hormone and luteinizing hormone mRNA were decreased significantly, while the expressions of ovarian follicle stimulating hormone and luteinizing hormone receptor mRNA were increased significantly. The expression of estrogen receptor mRNA in ovary and uterus was decreased significantly. Repeated immobilization stress may disrupt the estrous cycle by interfering with the endocrine regulation of the hypothalamic-pituitary-ovarian axis, thus damaging the gonadal and reproductive endocrine function of female animals.

Influence of ginsenoside Rb1 pretreatment on expression of brain derived neurotrophic factor in rat hippocampus after acute immobilization stress / 中国中西医结合急救杂志

Objective To investigate the effects of ginsenoside Rb1 pretreatment on the expression of brain derived neurotrophic factor (BDNF) in hippocampus of rat models under acute immobilization stress.Methods Eighteen Sprague-Dawley (SD) rats were randomly divided into three groups (each n =6):normal control group,acute immobilization stress model group,and ginsenoside Rbl group.The rats in acute immobilization stress model group and ginsenoside Rb1 group were exposed to acute immobilization for 2 hours.Thirty minutes before the modeling,ginsnoside Rb1 (40 mg/kg) was injected intraperitoneally into rats in the ginsenoside Rbl group,and the control group was not treated.The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of plasma cortisol (CORT) and adrenocorticotropic hormone (ACTH).The real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of BDNF mRNA in rat hippocampus and its expression of BDNF protein was measured by Western Blot.Results In acute immobilization stress model group,compared with those before modeling,the plasma CORT and ACTH concentrations were significantly higher after modeling [CORT (μg/L):3.79 ± 0.50 vs.2.06 ± 0.35,ACTH (μg/L):1.69 ± 0.12 vs.0.94 ± 0.12,both P ＜0.05];compared with the normal control group,the mRNA and protein expressions of BDNF in hippocampus in the acute immobilization stress model group were decreased significantly [BDNF mRNA (A value):42.87 ± 5.56 vs.109.39 ± 9.11,BDNF protein (grey value):0.94 ± 0.02 vs.1.02 ± 0.03,both P ＜ 0.01];compared with acute immobilization stress model group,the mRNA (113.73 ± 6.24 vs.42.87 ± 5.56) and protein expressions (1.04 ± 0.02 vs.0.94 ± 0.02) of BDNF in hippocampus of pre-treatment groups were significantly higher (all P ＜ 0.05).Conclusions The results suggest that pretreatment with ginsenoside Rb1 alleviate hippocampus lesion induced by acute immobilization stress through regulating the BDNF mRNA and protein expressions in hippocampus.

Effects of Immobilization Stress on Nitric Oxide Active Neurons in Rat’s dlPAG; Histochemical Study.

Background: Exposure to stress-factors caused an array of biochemical, physiological and behavioral changes. According to literature data, specific stressors may elicit specific responses, and different stressors may activate different brain systems by using specific pathways within the central nervous system. Several brain structures, including the periaqueductal gray (PAG), have been implicated in the functional neuroanatomy of stress response. The dorsolateral column of the periaqueductal gray (dlPAG) integrates aversive emotional experiences and represents an important site responding to life threatening situations. It was reported that nitric oxide (NO) affects the neuronal activity of the PAG. The goal of the present study was to investigate the changes of NO activity in the dlPAG of immobilized rats using a histochemical examination of the distribution of NADPH-d reactivity neurons. Our results showed that NO activity in rat’s dlPAG was significantly increased by acute immobilization stress. This suggests a pivotal role of this part of the brain and NO-ergic system in stress response which main role is to attenuate the effect of stress and to restore the homeostasis. Methods: The experiments were carried out on male Wistar rats (180-200g), divided into two groups. The first group represented intact controls. The second group was subjected to acute immobilization stress. Results: The acute stressor – 1 hour immobilization, showed statistically significant increase in the number of the NADPH-d positive neurons compared to the control group (p < 0.01). Conclusion: NO activity in rat’s dlPAG was significantly increased by acute immobilization stress.

Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 microg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Protective effect of Habenaria intermedia tubers against acute and chronic physical and psychological stress paradigms in rats

The present study was undertaken to evaluate the adaptogenic activity of ethanol (EtHI), ethyl acetate (EAHI) fractions of Habenaria intermedia D. Don, Orchidaceae (HI), tubers using immobilization induced acute stress (AS), chronic stress (CS) and swimming induced stress in experimental animals. The tested doses of EtHI (100 and 200 mg/kg, p.o.) and higher dose of EAHI (200 mg/kg, p.o.) normalized altered serum biochemical parameters and the severity of ulcers in both AS and CS. EAHI and EtHI restored the hyperthrophy of adrenal gland and atrophy of spleen and thymus gland in AS and CS. Greater swimming time was noted in the mice pretreated with EtHI and EAHI. Levels of adrenal ascorbic acid and cortisol were restored significantly. EAHI exhibited prominent scavenging effect of DPPH, hydroxyl radical and lipid peroxidation in vitro. Phytochemical studies resulted in the isolation of scopoletin and gallic acid as marker compounds. Our results proved the traditional claim of HI as anti-stress/adaptogen in Ayurvdea.

The Characteristics of Supramammillary Cells Projecting to the Hippocampus in Stress Response in the Rat

The hypothalamus-pituitary-adrenocortex (HPA) axis is the central mediator of the stress response. The supramammillary (SuM) region is relatively unique among the hypothalamic structures in that it sends a large, direct projection to the hippocampal formation. It has been shown that mild stress could activate the SuM cells that project to the hippocampus. However, the role of these cell populations in modulating the stress response is not known. The present study examined the effect of stress on different populations of SuM cells that project to the hippocampus by injecting the fluorescent retrograde tracer, fluorogold (FG), into the hippocampus and utilizing the immunohistochemistry of choline acetyltransferase (ChAT), corticotrophin releasing factor (CRF), serotonin (5-HT), glutamate decarboxylase (GAD), tyrosine hydroxylase (TH) and NADPH-d reactivity. Immobilization (IMO) stress (2 hr) produced an increase in the expression of ChAT-immunoreactivity, and tended to increase in CRF, 5-HT, GAD, TH-immunoreactivity and nitric oxide (NO)-reactivity in the SuM cells. Fifty-three percent of 5-HT, 31% of ChAT and 56% of CRF cells were double stained with retrograde cells from the hippocampus. By contrast, a few retrogradely labeled cells projecting to the hippocampus were immunoreactive for dopamine, gamma-aminobutyric acid (GABA) and NO. These results suggest that the SuM region contains distinct cell populations that differentially respond to stress. In addition, the findings suggest that serotonergic, cholinergic and corticotropin releasing cells projecting to the hippocampus within the SuM nucleus may play an important role in modulating stress-related behaviors.

Adaptogenic and in vitro antioxidant activity of flavanoids and other fractions of Argyreia speciosa (Burm.f) Boj. in acute and chronic stress paradigms in rodents.

Argyreia speciosa (sweet) (Burm.f.) Boj. is an Ayurvedic rasayana plant used as an adaptogen. The present study reports the investigations done on the adaptogenic property of ethanol (EtAS; 100 and 200 mg/kg; po), ethyl acetate (EAAS; 100 and 200 mg/kg; po) fraction and flavanoids such as quercetin and kaempferol (25 mg/kg; po) of the root. Immobilization induced acute stress (AS; 3 days) and chronic stress (CS; 7 days) and swimming induced stress models were used to screen the anti-stress effect of the plant fractions and isolated flavanoids. The tested doses of EtAS and isolated flavanoids were able to produce significant effects in normalizing altered serum biochemical parameters and the severity of ulcer in both AS and CS models. Higher dose of EtAS, quercetin and kaempferol (25 mg/kg; po) were found to be significant in restoring the hypertrophy of adrenal gland and atrophy of spleen and thymus gland only in CS model. Greater swimming time was noted in the mice pretreated with tested doses of flavanoids and EtAS. In addition, levels of adrenal ascorbic acid and cortisol were restored compared to stress control group. EtAS exhibited significant scavenging effect of DPPH, hydroxyl radical and LPO. Thus, EtAS, quercetin and kaempferol are capable of increasing the capacity to tolerate non-specific stress in experimental animals, as evident from restoration of large number of parameters in the stress models studied. Bioactivity of EtAS may be due to the synergetic action of isolated flavanoids. Improvement in stress markers may be due its prolong effect of resistance to stress and partly due to free radical scavenging activity.

The Effects of Puerariae Flos on Stress-induced Deficits of Learning and Memory in Ovariectomized Female Rats

Puerariae flos (PF) is a traditional oriental medicinal plant and has clinically been prescribed for a long time. The purpose of the present study was to examine the effect of PF on repeated stress-induced alterations of learning and memory on a Morris water maze (MWM) test in ovariectomized (OVX) female rats. The changes in the reactivity of the cholinergic system were assessed by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) in the hippocampus after behavioral testing. The female rats were randomly divided into four groups: the nonoperated and nonstressed group (normal), the sham-operated and stressed group (control), the ovariectomized and stressed group (OS), and the ovariectomized, stressed and PF treated group (OSF). Rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and PF (400 mg/kg, p.o.) was administered 30 min before IMO stress. Results showed that treatments with PF caused significant reversals of the stress-induced deficits in learning and memory on a spatial memory task, and also increased the ChAT immunoreactivities. In conclusion, administration of PF improved spatial learning and memory in OVX rats, and PF may be useful for the treatment of postmenopausal-related dementia.

Effect of immobilization stress on the expression of TH, BDH and CRH gene in rat brain

PURPOSE: Catecholamines are the neuro-transmitters in the sympathetic nervous system (SNS) and are activated by stress stimulus. Tyrosine hydroxylase (TH) and Dopamine-beta-Hydroxylase (DBH) are very important enzymes in the catecholamine synthesis. Corticotropin releasing hormone (CRH) is released in the process of reacting to stresses. The aim of this study is to find out what effects immobilization stresses have on the expression of TH, BDH and CRH mRNA in a rat's brains. METHODS: We compare expression levels in rat's brains of TH, DBH and CRH mRNA induced by immobilization stresses between the test group and controled group. The expression levels of TH, DBH and CRH mRNA are measured by RT-PCR and the Western Blotting Analysis (WBA). RESULTS: In brains and adrenal glands of the immobilization stress group, the expression levels of TH and DBH mRNAs are significantly two to three times higher (P<0.01), and CRH mRNAs are approximately one and a half times higher (P<0.05) than those of controlled group. CONCLUSION: This study suggest that the expression levels of TH, DBH and CRH mRNAs are activated by stress stimulus in a rat's brains and adrenal glands.

Effects of Quetiapine on the Immobilization Stress-induced BDNF and CRF Expression in Rat Brain / 대한정신약물학회지

OBJECTIVE: In this study we examined the effects of quetiapine on the immobilization stress-induced brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRF) expression in rat brain. We also assessed the antidepressant activity of quetiapine. METHOD: We used in situ hybridization to examine the effects of chronic administration of quetiapine in gene transcription. This study also examined the influence of quetiapine in an animal model of depression, the forced swimming test (FST). RESULTS: 1) Repeated immobilization stress (2 hr daily for 3 weeks) decreased mRNA levels of BDNF in the hippocampus (p<0.01), parietal cortex (p<0.01) and pyriform cortex (p<0.05). 2) Repeated immobilization stress increased mRNA levels of CRF in the hypothalamic paraventricular nucleus (PVN)(p<0.01). 3) Chronic quetiapine (10 mg/kg) treatment (daily for 3 weeks) alone significantly increased BDNF mRNA expression in the dentate gyrus of hippocampus when compared to controls under basal conditions (p<0.01), whereas no such effect was observed in the neocortex. 4) Chronic pretreatment of quetiapine also markedly increased the stress-induced decrease of BDNF mRNA expression in the hippocampus (p<0.01) and neocortex (p<0.01). 5) Moreover, the stress-induced elevation of CRF mRNA expression was blocked by chronic quetiapine pretreatment in PVN (p<0.01) although chronic quetiapine treatment alone did not significantly reduce CRF mRNA levels in comparison to controls under basal condition. 6) When rats received acutely quetiapine, quetiapine did reduce the immobility time at 10 mg/kg, as compared with the control group (p<0.05). CONCLUSION : These results suggest that quetiapine has not only potentially an antidepressant effect but also a neuroprotective action in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.

Characterization of Peroxiredoxins in the Gray matter in the spinal cord after Acute Immobilization Stress

PURPOSE: Many stresses produce reactive oxygen species and bring about mechanism of antioxidant reaction. Cytokine and a neurotransmitter through the cell membrane, as well as signal transduction through the cell membrane, are used for various pathological condition of the brain, such as neurodegenerative disease. There are several antioxidant enzymes in cells (superoxcide dismutase, glutathion peroxidasae, peroxiredoxin catalase, etc.) METHODS: This study used single- or double-label immunohistochemical techniques to analyze mouse spinal neuron cells expressing Prx I and Prx III after acute mobilization stress. RESULTS: Prx I was observed in dendritic cell of the gray matter of the spinal cord, and Prx III was observed in the cytoplasm of the GM of the spinal cord. CONCLUSION: The results of this study will help to explain differences of expression in the distributions of the peroxiredoxin enzymes of the spinal cord.

Characterization of Peroxiredoxins in the Gray matter in the spinal cord after Acute Immobilization Stress

PURPOSE: Many stresses produce reactive oxygen species and bring about mechanism of antioxidant reaction. Cytokine and a neurotransmitter through the cell membrane, as well as signal transduction through the cell membrane, are used for various pathological condition of the brain, such as neurodegenerative disease. There are several antioxidant enzymes in cells (superoxcide dismutase, glutathion peroxidasae, peroxiredoxin catalase, etc.) METHODS: This study used single- or double-label immunohistochemical techniques to analyze mouse spinal neuron cells expressing Prx I and Prx III after acute mobilization stress. RESULTS: Prx I was observed in dendritic cell of the gray matter of the spinal cord, and Prx III was observed in the cytoplasm of the GM of the spinal cord. CONCLUSION: The results of this study will help to explain differences of expression in the distributions of the peroxiredoxin enzymes of the spinal cord.

Effects of Chinese Herbs on Enkaphalin mRNA and Prodynorphin mRNA Gene Expression in Rat Hippocampus with Chronic Immobilization Stress / 中华中医药杂志

Objective: To investigate the mechanism of Chinese herbs in resisting chronic immobilization stress.Methods: The rat models of chronic immobilization stress were copied by merely constraint.Total RNA in hippocampus was extracted and primers of enkaphalin or prodynorphin were respectively added for RT-PCR reaction.Then the expressions of enkaphalin and prodynorphin in hippocampus were compared. Results: Enkaphalin mRNA and prodynorphin mRNA expressions in hippocampus markedly increased in chronic immobilization stress and the longer the more evident.Xiaoyao powder as well as decoction of four mild drugs were able to decrease the gene expression of enkaphalin mRNA,and all the three recipes were able to decrease the gene expression of prodynorphin mRNA,and the effect of Xiaoyao powder was obviously outweigh to Jinkuishenqi pill.Conclusion: enkaphalin and prodynorphin both participated in the regulation of hippocampus on stress;the regulation of endogenous opium system was one of the most important ways of the three recipes in accommodating stress.

Expression of Preadipocyte Factor-1 (Pref-1) and Vitamin D3 Up-regulated Protein 1 (VDUP1) Genes in Rat Adrenal Gland following Chronic Immobilization Stress / 대한해부학회지

Preadipocyte factor-1 (Pref-1) is expressed in the neuroendocrine organs such as the pituitary gland, the adrenal gland, the pancreas, the testis, etc. Vitamin D3 up-regulated protein 1(VDUP1) gene is known to be a novel member of early response genes as an oxidative stress mediator. The aim of the present study was to investigate whether Pref-1 and VDUP1 is involved in stress response in the adrenal gland following chronic immobilization stress. In situ hybridization for Pref-1 and VDUP1 genes (Pref-1 and VDUP1) was performed in the rat adrenal glands following immobilization stress, 2 hr once daily for 7 days. In situ hybridization analysis revealed that Pref-1 expression was up-regulated in rat adrenal medulla following chronic immobilization stress. However, Pref-1 was down-regulated in the zona glomerulosa of the adrenal cortex following chronic immobilization stress. VDUP1 expression was up-regulated in the zona glomerulosa and the adrenal medulla following chronic immobilization stress. These results show that Pref-1 and VDUP1 may be novel genes responding to chronic immobilization stress in adrenal gland.

The Effects of Immobilization Stress on the Ultrastructure of Rat Atrial Myocytes / 체질인류학회지

This study was performed to investigate the subcellular changes of rat atrial muscle cells by immobilization stress. Sprague -Dawley rats weighting 200 gm were immobilized in small round plastic tube for 2, 6, 12, and 24 hours respectively. The atrial tissue obtained from each animals were observed by transmission electron microscopes. In the heart of rat subjected 2 hours immobilization stress no significant morphological changes were found in electron microscopy, similarly as in control animal. After 6 and 12 hours immobilization stress, the following electron -microscopic changes of atrial myocytes were observed at the swelling of mitochondrial matrix with disturbance in cristea, focal loss of cytoplasmic matrix, vacuoles with myeline -like structure, apoptotic changes of myocytes, focal widening of intercalated disc interspace and lysis of myofibrils. After 24 hours immobilization stress, very small sized mitochondria, similarly as small sized secretory granules and various sized granules are observed in the perinuclear region of atrial myocytes. Atrial specific granules are moved centripetally toward the central region of the atrial myocytes after immobilization stress. Above results will be aid in understanding the structures of atrium with dual function of blood circulation and endocrine, and in research of modulation of secretory granules in atrial muscle cells.

Morphological Observations on the Changes of Membrane Permeability by Immobilization Stress in the Rat Atrial Myocyte / 대한해부학회지

This study was performed to investigate the effect of immobilization stress on the ultrastructural changes and membrane permeability in rat atrial myocyte using immunohistochemical and lanthanum tracer techniques. Male Sprague-Dawley rats, body weight 160~200 g, were used for all immobilization stress group. Rats were immobilized in small round plastic tube for 6, 12 or 24 hours, except for the control group. Alterations of myocardial myoglobin and alpha-actinin as well as membrane permeability after immobilization stress were examined by immunohistochemistry, and lanthanum permeability of the rat atrial myocyte were observed by electron microscopy. In the control group, there was no loss of myoglobin or alpha-actinin from the atrial myocytes. After 6 and 12 hours immobilization stress, the loss of myoglobin and alpha-actinin could be identified the atrial myocytes. In the 24 hour immobilization groups, the content of the myoglobin and alpha-actinin recovered partially. Lanthanum was deposited only in the intercellular space of the atrial myocardium in the control group. In the 6 hour immobilization group, the atrial myocytes showed severe ultrastructural changes during immobilization stress. Lanthanum deposited in the sarcoplasm, myofibrils, adjacent of mitochondria, and mitochondrial matrix. In the 12 or 24 hour immobilization groups, the morphological alteration of atrial myocytes appeared weekly. In the 12 hour group, lanthanum deposited in myofibrils, adjacent of mitochondria and in the mitochondrial matrix. In the 24 hour group, lanthanum deposited mainly in intercellular space of atrial myocardium, and rarely in the sarcoplasm of myocytes. These results suggest that the immobilization stress may induce the alteration of cardiac cell membrane permeability and the ultrastructures of atrial myocardium.

The Effect of Immobilization Stress and Corticosterone on Haloperidol-induced c-fos Expression in Rat Brain / 대한정신약물학회지

OBJECTIVE: Immediate early gene (IEG), c-fos is known to encode a 62 kDa nuclear protein (Fos) which has a critical role in the stimulus response process of many cells. c-fos can be activated in the central nervous system by a variety of physiological and pharmacological treatment. Recently evidences has been reported suggesting that glucocorticoid hormones, which are released from adrenal cortex in response to stress, may regulate IEG expression. We observed whether immobilization stress or corticosterone altered the induction of c-fos by haloperidol in the nucleus accumbens, lateral striatum, and prefrontal cortex. METHODS: Twenty-four healthy Wistar rats of male sex, weighing 300-450 g, were divided into 6 groups according to injection agents [vehicle (1 mg/kg), haloperidol (1 mg/kg), corticosterone (1 mg/kg), immobilization stress, haloperidol (1 mg/kg) and corticosterone (1 mg/kg), haloperidol (1 mg/kg) and immobilization stress] respectively. Fos-immunoreactivity was measured by counting of Fos-positive neurons in the nucleus accumbens, lateral striatum, and prefrontal cortex. RESULTS: (1) The number of Fos-positive neurons in the nucleus accumbens was significantly decreased in the haloperidol plus immobilization stress group and haloperidol plus corticosterone group compared with that in the haloperidol group (p<0.05). (2) The number of Fos-positive nurons in the lateral striatum was significantly decreased in the haloperidol plus corticosterone group compared with that in the haloperidol group, but the number of Fos-positive neurons in the lateral striatum was not significantly different between the haloperidol plus immobilization stress group and the haloperidol group (p<0.05). (3) The number of Fos-positive neurons in the prefrontal cortex was significantly increased in the haloperidol plus immobilization stress group and haloperidol plus corticosterone group compared with that in the haloperidol group (p<0.05). CONCLUSION: These results suggest that regulatory process exerted by corticosterone may alter the antipsychotic effect of haloperidol.

Effects of Ginseng Saponin on the Stress-Induced Plasma Corticosterone Levels in Mice / 신경정신의학

OBJECTIVES: The present study was designed to investigate the effect of ginseng saponin and its major active metabolite on the HPA axis under acute stress-i.c.v. injection stress, and immobilization stress, and to examine whether nitric oxide is involved in the mechanism of ginseng saponin on the HPA axis under acute stress. METHODS: In the experiment to study the effect of ginseng on HPA axis during stress, various dose of GTS were injected intracerebroventricularly(i.c.v.) or intraperitoneally(i.p.). Plasma corticosterone levels were measured 30 min after the i.c.v. injection stress. Immobilization stress was applied for 30 min and then blood was cellected for the assays of plasma corticosterone levels immediately after the completion of immobilization stress. To determine the active ginsenosides that can affect the stressinduced plasma corticosterone levels, various dose of each gisendosides(Rb1, Rb2, Rc, Re, Rf, Rg1, 20(S)-Rg3, and 20(R)-Rg3) were injected i.c.v. or i.p.. In the experiment to determine the involvement of the nitric oxide in the inhibitory effect of ginseng on the HPA, NG-Nitro-L-arginine methyl ester(L-NAME) and ginsenosides were coadministered i.c.v. or i.p., and plasma corticosterone levels were measured 30 min after stress was applied. RESULTS: First, the present study showed that ginseng total saponin, ginsenoside Rg3(S form), and ginsenoside Rc administered i.c.v. attenuated the intracerebroventricular injection stress-induced increase in plasma corticosterone levels, and these effects were removed by nitric oxide co-injection. Second, ginseng total saponin and ginsenoside Rc administered i.p. attenuated the immobilization stress-induced increase in plasma corticosterone levels, but ginsenoside Rg3(S form) did not attenuate the immobilization stress-induced increase in plasma corticosterone levels. The attenuative effects of ginseng total saponin and ginsenoside Rc in the immobilization stress-induced increase in plasma corticosterone levels were not affected by L-NAME co-injection. CONCLUSION: This study suggests that ginseng saponin attenuated stress-induced increase in plasma corticosterone levels and these effects were mediated by different mechanisms according to the components of ginseng saponin, and routes of administration.

The functional changes of splenic lymphocytes in immobihzation stress mice / 中国免疫学杂志

Objective: To study the affection of immobilization stress (IMS) on mice splenic lymphocytic function. Methods:The proliferation of lymphocytes was examined by MTT, and intracellular[Ca2+] was examined by fluorescence probe, Fura-2/AM, membrane of lymphocytes IL-2 receptor(mIL-2R) and cell cycle were examined by flow cytometry. Results;The end of IMS was found to be the lowest proliferation response after IMS, at the same time mIL-2R expression was impaired. Analysis of cell cycle showed the proliferation of splenocytes from IMS mice might be bloched in G2/M phases. Intracellular[Ca2+] was significant increased after IMS. Conclusion: IMS may induce the disfunction of lymphocytes and immunosuppression.