• Journal of Veterinary Clinics
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• v.31 no.5
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• pp.394-402
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• 2014

The objective of this study was to investigate the effect of chronic unpredictable stress on the reproductive function and ovarian luteinizing hormone receptor (LHR) expression. 9-week-old C57BL/6 female mice were randomly divided into two groups: control group and stressed group. Mice have been stressed twice a day for 35 days with 12 different stressors which were randomly selected. The results demonstrate that there is significant increase in the anxiety-related behaviors (P < 0.05), decrease body weight gain rate (P < 0.01) and decrease in the average of litter size in stressed mice compared with control group (P < 0.01). Furthermore, the rate of primary, secondary and early antral follicles in stressed mice significantly decreased (P < 0.05), whereas that of atretic follicles significantly increased compared with control mice (P < 0.01). The immunohistochemical analysis revealed that reduced LHR expression in granulosa cells of follicle and luteal cells of corpus luteum in response to chronic unpredictable stress. The western blot analysis revealed significantly decrease in LHR expression in the stressed mice ovaries compared with the control (P < 0.05). These results suggest that ovarian LHR expression affected by chronic unpredictable stress and the modulated ovarian LHR is responsible for ovarian follicular maldevelopment and reproductive dysfunction.

• Journal of Korean Biological Nursing Science
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• v.25 no.1
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• pp.280-320
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• 2023

Purpose: This study was conducted to assess the antidepressant effects of capsaicin in chronic depressive rats and elucidate the mechanism underlying its effects. Methods: Male Wistar rats (280~320 g, 8 weeks of age) were subjected to depression induced by chronic unpredictable mild stresses. The rats were exposed to 8 kinds of stresses for 8 weeks. In the last 2 weeks, fluoxetine or capsaicin was injected subcutaneously. The dose of fluoxetine was 10 mg/kg (body weight), while the doses of capsaicin consisted of low (1 mg/kg), middle (5 mg/kg), and high (10 mg/kg). The forced swim test (FST) was conducted to evaluate the immobility time of rats. The immobility time indicates despair, one of symptoms of depression. The change of tryptophan hydroxylase (TPH) in the dorsal raphe was investigated using immunohistochemistry. In the hippocampus cornu ammonis (CA) 1 and 3, glucocorticoid receptor (GR) expression was measured. Results: The immobility time in the FST was significantly lower (p < .05) in the low-dose (M = 32.40 ± 13.41 seconds) and middle-dose (M = 28.48 ± 19.57 seconds) groups than in the non-treated depressive rats (M = 90.19 ± 45.34 seconds). The amount of TPH in the dorsal raphe was significantly higher (p < .05) in the middle-dose (M = 249.17 ± 35.02) and high-dose (M = 251.0 ± 56.85) groups than in the non-treated depressive rats (M = 159.78 ± 41.16). However, GR expression in the hippocampus CA1 and CA3 did not show significant differences between the non-treated depressive rats and the capsaicin-injected rats. Conclusion: This study suggests that capsaicin produces an antidepressant-like effect on chronic unpredictable mild stress-induced depression in rats via the serotonin biosynthesis pathway.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.552-560
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• 2023

Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

• Journal of Oriental Neuropsychiatry
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• v.13 no.2
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• pp.107-119
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• 2002

This study was performed to evaluate the effects of Koamsimsinwhan (without Cinnabarite) on depression in CMS-treated rats. Rats of trial groups were exposured to chronic mild unpredictable stress for 4 weeks. These CMS-treated rats were stratified into Koamsimsinwhan(without Cinnabarite) group and vehicle(non-drug) group. And there were control rats excluding both CMS and Koamsimsinwhan(without Cinnabarite). Forced swimming test, general activity test and immunohistochemical test(measuring the level of manifestation of c-Fos in PVN) were executed to evaluate the effects of Koamsimsinwhan(without Cinnabarite) on depression after 4 weeks of CMS treatment. The results were as follows 1. In FST, depression was induced from CMS treatment and was supressed with Koamsimsinwhan(without Cinnabarite). 2. The increased activity of nerve cell in PVN, which refers to stress, was induced from CMS treatment and normalized with Koamsimsinwhan (without Cinnabarite).

• Journal of Oral Medicine and Pain
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• v.31 no.1
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• pp.79-89
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• 2006

The aim of this study is to know how the rat submandibular gland changes under various emotional stress condition, using molecular biological methods. Restraint and chronic unpredictable mild stress (CUMS) experiment is conducted on fifty one 7-week old Sprague-Dawley rats (restraint stress experiment: 21, CUMS: 30). The rats were sacrificed, the submandibular glands were excised immediately at certain time, and examined by the use of immunohistochemistry and western blotting. In CUMS experiment, sucrose preference test, water intake change, weight change were implemented at 1 week interval for the experimental period The results are as follows: 1. The number of clusterin-secreting cells of restraint stress group compared to control group showed significantly decreasing tendency in all experimental groups except for the 1st hour group (p<0.001 in the 9th, 24th, 72nd, 120th, and 168th hour group). 2. The number of clusterin-secreting cells of CUMS group compared to control group showed significantly increasing tendency in the 2nd week group (p<0.01), and significantly decreasing tendency in the 4th and 5th week group (p<0.001). 3. Sucrose preference test in CUMS experiment showed significant difference between the 5th week experimental group and control group (p<0.01). 4. Weight change in CUMS experiment showed significant difference between the 5th week experimental group and control group (p<0.01), but water intake change didn't show significant difference compared to control group. 5. In western blot analysis, clusterin expression was decreased on a gradual basis in due time compared to the control group in the restraint stress group. As for CUMS group (chronic unpredictable mild stress group), it was increased till the 2nd week and decreased till the 5th week after that, which is similar to immunohistochemical analysis result and the decreasing tendency of sucrose preference and weigh changes. Through the test, it was proved that expression of clusterin in saliva glands decreases after receiving either acute or chronic stress, indicating relation with depression caused by chronic stress. Unlike other data, however, apoptotic tendency was hardly found in tissues. Diverse possibilities could be suggested on that: first, the stress was not enough to expedite apoptosis; second, apoptosis-related protein was already being secreted though not detected with microscope; third, clusterin, a major secretion molecule of saliva, decreased with saliva's malfunction due to stress. In the respect, it will be necessary to examine proteins expressed in case of cell death or other heat-shock proteins at the same time, in order to see whether any cellular change or death is caused by decreasing clusterin under high stress, and whether the original state is restored as time goes by under mild stress, through longer-term tests using even higher acute stress.

• Journal of Oriental Neuropsychiatry
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• v.12 no.2
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• pp.53-68
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• 2001

This study was performed to investigate the anti-depression effect of Guibiondamtang in rat model of depression. The rats in the experiment were stratified into 3 groups, ie, Guibiondamtang, saline, normal (non-stressed) groups. Chronic exposure to mild unpredictable stress such as white noise, flashing lights and restriction of food and water, causes the behavioral symptoms correspondent to depression. Consumption of 1% sucrose solution fell in rats exposed to CMS for 4 weeks. In the open field test , the exploratory activity ie. locomotion and centering decreased after CMS. We then evaluated the sucrose consumption and activity during 4 weeks of treatment with experimental drugs. The results were as follows: 1) There was no relation between sucrose intake and weight. 2) The Guibiondamtang(歸脾溫膽湯) group reinstated sucrose consumption within 5-6 weeks while having no influence on sucrose intake in normal group. 3) The Guibiondamtang(歸脾溫膽湯) group restored some exploratory activity in the open field test. 4) The Guibiondamtang-group had a-reduced potentiated startle response.

• Journal of Oriental Neuropsychiatry
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• v.28 no.3
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• pp.231-248
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• 2017

Objectives: This study evaluates anti-stress and sleep-inductive effects of Dongshingihyeolyangsubang (DSGYSB) on rats induced by chronic mild stress (CMS). Methods: Twenty-five healthy rats were randomly divided into five groups: normal, CMS (Control), DSGYSB50, DSGYSB100, and DSGYSBS200. All rats except the normal group were exposed to unpredictable stress conditions such as water deprivation, empty bottles, and forced treadmill. A week after starting the experiment, rats in DSGYSB50, DSGYSB100, and DSGYSB200 groups were fed orally with water once a day for two weeks. Then blood samples were taken from the rats for analysis of complete blood count, AST, ALT, and glucose. Noradrenaline, corticosterone, serotonin, GABA and melatonin were measured by ELISA kit. BDNF, CREB, TrkB and $TNF-{\alpha}$ were measured by RT-PCT. Results: In Noradrenaline contents, the DSGYSB200 group revealed significant decrease compared to the control group. In corticosterone contents, the DSGYSB200 group revealed significant decrease compared to the control group. In serotonin contents, the DSGYSB200 group revealed significant increase compared to the control group. In GABA contents, the DSGYSB50, DSGYSB100, and DSGYSB200 groups revealed significant increase compared to the control group. In the activity of BDNF, the DSGYSB50, DSGYSB100 and DSGYSB200 groups revealed significant increase compared to the control group. In the activity of CREB, the DSGYSB100 and DSGYSB200 groups revealed a significant decrease compared to the control group. In the activity of TrkB, the DSGYSB100 and DSGYSB200 groups revealed significant decrease compared to the control group. In the activity of $TNF-{\alpha}$, DSGYSB100 and DSGYSB200 groups revealed significant decrease compared to the control group. In glucose contents, the DSGYSB100 and DSGYSB200 groups revealed significant decrease compared to the control group. In the leukocyte changes, white blood cells, neutrophil, lymphocytes, and monocyte significantly increased in the DSGYSB100 and DSGYSB200 groups than the control group. In the erythrocyte changes, hemoglobin significantly increased in the DSGYSB200 group than the control group. Conclusions: Results suggest that Dongshingihyeolyangsubang has anti-stress and sleep-inductive effects on rats induced by CMS.

• Journal of Oriental Neuropsychiatry
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• v.13 no.2
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• pp.121-147
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• 2002

This study was performed to evaluate the effects of Quibitang in the chronic mild stress(CMS) model of depression in rats. Chronic exposure to mild unpredictable stress was found to depress the consumption of sucrose solution in rats for 8 weeks. These CMS-treated rats were stratified into Quibitang gruop and saline group. And control rats were also stratified into Quibitang group and saline group. The change of the consumption of sucrose solution and the body weight were measured, and open field test, elevated startle response and plus maze test were performed, to investigate the anti-depression effect of Quibitang. The results were as follows: 1. The consumption of sucrose solution was significantly reversed in Quibitang-treated group at 9th, 11th, 12th week, but there was no significant change at 10th week 2. CMS schedule decreased body weight. CMS-treated groups showed decrease of body weight after 5 weeks. After 10 weeks, Quibitang group showed lower body weight than saline group in CMS-treated groups 3. In open field test, Quibitang group showed significant difference of locomotion, latency. 4. In elevated startIe test, Quibitang group showed no significant change of startle response. 5. In plus maze test, Quibitang group showed no significant change of plus maze-time and plus maze-error.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.237-245
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• 1997

The study was designed to evaluate the significant roles of SSRI in rat of depression model. Chronic exposure to mild unpredictable stress has been found to depress the consumption of sweet 1% sucrose solutions in the Sprague-Dawley rats. We applied the variety of 11 types of stress regimens and identified depressive behaviours(developed by Willner) in 70 Sprague-Dawley rats. Rats in experiments were stratified into 6 groups, ie ; 3 kinds of SSRI(paroxetine, fluoxetine, sertraline), clomipramine, choline and saline control. Memory function was evaluated by passive avoidance learning and retention test. The authors determined how long memory retention would remain improved with 24 hour, 1 week, 2 weeks, 3 weeks, and 4 weeks at training-testing interval in depressive states of the Sprague-Dawley rats. The results were as follows ; 1) There were no significant differences between the 6 groups at the 24 hour training-testing interval. 2) The paroxetine treated group showed significant differences from the control group at the 1 week and 2 weeks training-testing interval. 3) The paroxetine and the fluoxetine treated groups showed singificant differences from the control group at 3 week training-testing interval. 4) The paroxetine and the choline treated groups showed significant differences from the control group at 4 week training-testing interval. In summary, paroxetine had an effect on long term memory processing from 1st week to 4th week. Also, fluoxetine(at 3rd week) and choline(at 4th week) had effect on long term memory processing. Sertraline, clomipramine were ineffective on memory processing during 4 weeks observation. Possible explanations why paroxetine had early effect on memory processing than the other selective serotonin reuptake inhibitors are rapid bioavailability, which is the characteristics of pharmacokinetics of paroxetine. In clinical situation, author carefully suggest that SSRI would be beneficial to improve the memory function caused by depressive neurochemical changes.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.376-386
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• 2022

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.