• Journal of Korean Biological Nursing Science
• /
• v.18 no.1
• /
• pp.36-42
• /
• 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.

• Biomedical Science Letters
• /
• v.15 no.3
• /
• pp.249-255
• /
• 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
• /
• v.22 no.5
• /
• pp.708-720
• /
• 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.

• Journal of Microbiology and Biotechnology
• /
• v.22 no.3
• /
• pp.422-430
• /
• 2012

Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxiety-like behaviors and alters the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamic-pituitary-adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.

• Journal of the Korean society of biological therapies in psychiatry
• /
• v.24 no.3
• /
• pp.129-141
• /
• 2018

Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall into sorrow and suffering therefore this suicide is a huge loss to family and society. There have been attempts to reduce and prevent suicide by understanding the mechanism of suicide. The mechanism of suicide can be thought of as psychological mechanism and biological mechanism. In the past, if we considered the psychological and biological mechanisms separately, the development of neuroscience now connects and integrates these two. Psychological factors affect biological factors and biological temperaments also affect perception or thinking about the situation and increase psychological vulnerability. Distant factors in suicidal behavior-such as childhood adversity and family and genetic predisposition-increase the lifetime risk of suicide. They alter the response to stress and other processes through changes in gene expression and regulation of emotional and behavioral characteristics. Distant factors affect the biological system and consequently changes in these systems can increase the risk of suicide. In other words, the distal factor does not directly induce suicidal behavior but rather acts indirectly through developmental or mediating factors. These mediating factors are impulsive aggressive and anxious trait, and chronic use of substances. The mechanism of this disorder is the abnormality of the serotonin system and the abnormality of the lipid level. Proximal factors are associated with the onset of suicide events and include changes in the major neurotransmitter systems, inflammatory changes, and dysfunction of glial cells in the brain. A series of studies, including a variety of research methods and postmortem and in-vivo imaging studies, show the impairment of the serotonergic neurotransmitter system and hypothalamic-pituitary-adrenal axis stress response system for suicidal behavior. These disorders lead to suicidal behavior due to difficulty in cognitive control of mood, pessimism, reactive aggression, abnormality in problem solving abilities, excessive response to negative social signals, severe emotional distress, and cognitive dysregulation of suicidal ideation.

• Journal of Oriental Neuropsychiatry
• /
• v.32 no.2
• /
• pp.111-127
• /
• 2021

Objectives: To review and analyze clinical and preclinical evidence of effectiveness, safety, and underlying mechanisms of yokukansan (YKS), a herbal medicine, in alleviating aggression. Methods: Classical records on YKS were searched in the Korean Traditional Medicine Knowledge Database (KTMKD). By searching five electronic databases, prospective clinical studies and preclinical studies of YKS for alleviating aggression/agitation published up to March 30, 2021 were included. Results: Only two classical records on YKS were found from the KTMKD. A total of 11 clinical studies and 15 preclinical studies were found from the five electronic databases. Among 11 clinical studies, seven enrolled patients with dementia and four enrolled patients with other neuropsychiatric disorders. Most clinical studies reported significant improvement in one or more outcomes related to aggression in the YKS group after treatment. Among 15 preclinical studies, all studies except two reported a significant decrease in aggression/agitation-related behavior of YKS or yokukansankachimpihange. Suggested underlying mechanisms of YKS or yokukansankachimpihange for aggression/agitation in these studies included regulation of serotonin receptor, amelioration of abnormal glucocorticoid level related to the hypothalamic-pituitary-adrenal axis, regulation of orexin secretion, amelioration of degeneration in brain cells including glia cells, and suppression of excessive glutamatergic or dopaminergic activity. Conclusions: There were some clinical and preclinical evidence supporting the effectiveness and safety of YKS for alleviating aggression. Given that aggression is the most frequent and destructive symptoms of behavioral and psychological symptoms of dementia, applicability of YKS as a herbal medicine should be further investigated in future high-quality research.

• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.77-83
• /
• 2024

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ_25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ_25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ_25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ_25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ_25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ_25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

• Korean Journal of Biological Psychiatry
• /
• v.3 no.2
• /
• pp.288-294
• /
• 1996

Background : Most studies of the pituitary hormonal responses to electroconvulsive therapy(ECT) have used limited blood sampling schedules. Little is known about the precise sequence of neuroendocrine events immediately following en ECT application. or about the regulation of the hormonal responses. Methods : Blood was sampled at three minute intervals from eleven patients(two schizophrenics and nine affective disorder patients) undergoing ECT. Each sample was immunologically assayed for arginine vasopressin(AVP), adrenocorticotropic hormone(ACTH), prolactin(PRL), and cortisol. Baseline hormone concentrations and several measures of response were determined for each hormone. The temporal and quantitative relationships among the hormonal responses were determined. Correlations were calculated between seizure duration and secretory responses. Results : All four hormones demonstrated significant secretory responses to ECT, with AVP increasing from 1.2 to 33.3pg/ml(P<0.001), ACTH from 5.4 to 32.3fmol/ml(P<0001). PRL from 21.8 to 102.2ng/ml(P<0.005) and cortisol from 20.1 to 31.1ug/dl(P<0.001). The three pituitary hormones showed consistent time courses of secretion with onset of responses by three minutes but clearly differing peak times of 3, 6, and 12-15 minutes for AVP, ACTH, and PRL, respectively. Cortisol began to rise after 6minutes and pecked between 20-30minutes. There ware no significant correlations between seizure duration and any of the secretory response measures. Conclusions : 1) The pituitary hormone response to ECT is sequential rather than synchronous 2) The AVP response was extremely rapid and more massive than those of any other hormones. 3) The ACTH response of this study was more rapid and mare robust than thai revealed by the mast of past studies. 4) The results strongly suggest that the pituitary hormones are released as a result of the seizure rather tho, the electrical stimulus. 5) The sequential pattern of responses suggests that neuroendocine feedback-regulatory mechanisms determine the response profile.

• Clinical and Experimental Pediatrics
• /
• v.49 no.3
• /
• pp.292-297
• /
• 2006

Purpose : In medulloblastoma, craniospinal radiation therapy combined with chemotherapy improves the prognosis of tumors but results in significant endocrine morbidities. We studied the endocrine morbidity, especially growth pattern changes. Methods : The medical records of 37 patients with medulloblastoma were reviewed retrospectively for evaluation of endocrine function and growth. We performed the growth hormone stimulation test in 16 patients whose growth velocity was lower than 4 cm/yr. Results : The height loss was progressive in most patients. The height standard deviation score (SDS) decreased from $-0.1{\pm}1.3$ initially to $-0.6{\pm}1.0$ after 1 year(P<0.01). Growth hormone deficiency(GHD) developed in 14 patients. During the 2 years of growth hormone(GH) treatment, the improvements of height gain or progressions of height loss were not observed. Twelve patients(32.4 percent) revealed primary hypothyroidism. One of six patients diagnosed with compensated hypothyroidism progressed to primary hypothyroidism. Primary and hypergonadotropic hypogonadism were observed in two and one patients respectively. There was no proven case of central adrenal insufficiency. Conclusion : Growth impairment developed frequently, irrespective of the presence of GHD in childhood survivors of medulloblastoma. GH treatment may prevent further loss of height. The impairment of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroidal axis is less common, while central adrenal insufficiency was not observed.

• Development and Reproduction
• /
• v.5 no.1
• /
• pp.73-79
• /
• 2001

Recently many studies have reported that total and bioavailable androgens reduced in male and female athletes and that physical exercise reduces the body weight and increases the reproductive abnormalities such as oligomenorrhea, anovulation, inadequate luteal phase, and delayed puberty in women by the inhibition of the hypothalamic-pituitary-gonadal (HPG) axis . In addition, high mileage endurance 겨nning, psychological stress, and military endurance training in men also reduce the secretion of reproductive hormones. To investigate the efffcts of physical endurance exercise on the secretion of reproductive hormones in men, androgenic hormones from adrenal glands and testis were measured in serum by the conventional radioimmunoassays after long-term (more than3 months), short-term (1 week), and acute (1${sim}$2 hours) physical exercises. Androgenic hormones from adrenal glands and testis such as total testosterone (TT), free testosterone (fT), dehydroepiandrosterone (DHEA), and androstenedione (A) decreased after thesestrenuous endurance trainings, whereas ACTH, cortisol, and dehydroepiandrosterone sulfetes (DHEAS) increased. Conadotropins (LH and FSH) were not idluenced by the physical exercises. Based upon the present results, we assume that the decrease in adrenal and testicular androgens by physical endurance exercises might be associated with the reproductive abnormalities in athletes by unknown factor(s) in addition to the HPG axis disturbance.