• Journal of Animal Reproduction and Biotechnology
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• v.34 no.1
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• pp.40-49
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• 2019

Chronic and unpredictable stress can disrupt the female reproductive system by suppression for secretion of gonadotrophin-releasing hormone (GnRH) and gonadotrophin, resulted in ovarian malfunction and infertility. In the recent days, kisspeptin has been highly highlighted as a hypothalamic peptide which directly stimulates synthesis and release for GnRH. However, in spite of the key role of kisspeptin in the female reproductive system, little information is still available on the changes of its expression during ovarian cycle under stressed condition. Therefore, we induced chronic and unpredictable stress series to the female mice to analyze kisspeptin expression in the brain and ovary. Stressed mice exhibited changes of behavior and body weight gain during the stress assessment, which suggested that the present stress model in mice was successfully established. In the brain level, kisspeptin expression was attenuated than control. In the ovary level, the stressed mice displayed irregularly shrunk oocytes with broken zona pellucida throughout the follicle stages, pyknotic granulosa cells, decreased number of developing follicles and increased number of atretic follicles than the control. In case of kisspeptin expression in the whole ovary tissue, the expression level was decreased in the stressed mice. In detail, the less intensity of kisspeptin expression in the antral follicles phase was observed in the stressed mice than control mice, indicating that local function of kisspeptin during ovary cycle is highly associated with development of ovarian follicles. We expect that the present study has important implications for the fields of reproductive biology.

• Mass Spectrometry Letters
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• v.14 no.3
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• pp.91-103
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• 2023

As one of the most common mood disorders, numerous studies have shown depression is the main risk factor for non-suicidal self-harm. The pathogenesis of depression is complex, and a comprehensive and rapid measurement of monoamine neurotransmitters and their metabolites will be very helpful in understanding the pathogenesis of depression. Therefore, a rapid and sensitive underivatized liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous monitoring of the levels of ten neurotransmitters and their metabolites in rat serum and limbic system and successfully applied to quantify the changes of neurotransmitter levels in chronic unpredictable mild stress-induced rats. The analytes studied were mainly involved in tyrosine metabolism, tryptophan metabolism, and glutamate cycling pathways, which are important in the pathogenesis of depression. It had been verified the method was sensitive and effective, with satisfactory linearity, and met the requirements of biological sample determination. Levels of neurotransmitters in rat serum, hippocampus, amygdala, prefrontal cortex, striatum, and hypothalamus were determined via the method. The results showed serotonin, dopamine, norepinephrine, and their metabolites were decreased, glutamine was increased, and glutamate was disturbed in chronic unpredictable mild stress-induced depression rats. This method provides a new approach to studying the pathogenesis of depression and other neurological disorders.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.245-250
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• 2015

Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.291-297
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• 2016

Cytisine (CYT), a partial agonist of ${\alpha}4{\beta}2-nicotinic$ receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.263-268
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• 2014

The etiology of most psychiatric disorders is still incompletely understood. However, growing evidence suggests that stress is a potent environmental risk factor for depression and anxiety. In rodents, various stress paradigms have been developed, but psychosocial stress paradigms have received more attention than non-social stress paradigms because psychosocial stress is more prevalent in humans. Interestingly, some recent studies suggest that chronic psychosocial stress and social isolation affects mainly anxiety-related behaviors in mice. However, it is unclear whether chronic non-social stress induces both depression- and anxiety-related phenotypes or induces one specific phenotype in mice. In the present study, we examined the behavioral consequences of three chronic non-social stress paradigms: chronic predictable (restraint) stress (CPS), chronic unpredictable stress (CUS), and repeated corticosterone-HBC complex injection (RCI). Each of the three paradigms induced mild to severe depression/despair-like behaviors in mice and resulted in increased immobility in a tail suspension test. However, anxiety-related phenotypes, thigmotaxis and explorative behaviors, were not changed by the three paradigms. These results suggest that depression- and anxiety-related phenotypes can be dissociated in mouse stress models and that social and non-social stressors might affect brain circuits and behaviors differently.

• Food Science of Animal Resources
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• v.40 no.1
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• pp.145-153
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• 2020

Depression is a kind of mood disorder characterized by decline in motivation, interest, attention, mental activity, and appetite. Although depression is caused by a variety of causes, including genetic, endocrine and environmental stress, mild depression has been reported to improve with diet. Therefore, various type of food sources including functional and nutritional supplement are required to treat the depressive patients. Cheese contains bioactive peptides that have beneficial effects on host health. In particular, Jersey milk has been reported to contain higher solids than does Holstein milk. This study investigated the effects of Gouda cheese from Jersey and Holstein milk on chronic, unpredictable, mildly stressed (CUMS) mice. Here, spontaneous alterations in cheese-fed stressed mice were noted to be effectively recovered with statistical significance regardless cow species. Interestingly, for the analysis of fecal microbiota, Bacteroidetes were noted to increase with a reduction in Firmicutes at the phylum level with Jersey cheese. Taken together, we suggest that cheese intake provided a beneficial effect on stressed mice in recovering recognition ability. In particular, changes in internal microbiota were observed, suggesting that the bioactive ingredients in cheese act as improvement agents with respect to mood and brain function.

• Food Science of Animal Resources
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• v.43 no.6
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• pp.1044-1054
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• 2023

Growing evidence indicates a crucial role of the gut microbiota in physiological functions. Gut-brain axis imbalance has also been associated with neuropsychiatric and neurodegenerative disorders. Studies have suggested that probiotics regulate the stress response and alleviate mood-related symptoms. In this study, we investigated the effects of the probiotic Lacticaseibacillus rhamnosus IDCC3201 (L3201) on the behavioral response and fecal metabolite content in an unpredictable chronic mild stress (UCMS) mouse model. Our study shows that chronic stress in mice for three weeks resulted in significant changes in behavior, including lower locomotor activity, higher levels of anxiety, and depressive-like symptoms, compared to the control group. Metabolomic analysis demonstrated that disrupted fecal metabolites associated with aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis by UCMS were restored with the administration of L3201. Oral administration of the L3201 ameliorated the observed changes and improved the behavioral alterations along with fecal metabolites, suggesting that probiotics play a neuroprotective role.

• 축산식품과학과 산업
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• v.9 no.2
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• pp.58-65
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• 2020

우울증은 동기, 의욕, 관심, 주의력, 정신기능 및 식욕의 감소를 특징으로 하는 일종의 기분 장애이다. 우울증은 유전적, 내분비 및 환경적 스트레스를 포함한 다양한 원인에 의해 발생하지만 가벼운 우울증은 식이요법으로 개선되는 것으로 보고되었다. 따라서 우울증 환자를 치료하기 위해서는 기능성 및 영양 보충제를 포함한 다양한 식품 공급원이 필요하다. 치즈에는 숙주 건강에 유익한 영향을 미치는 생리 활성 펩타이드가 포함되어 있다. 특히 저지(Jersey) 우유는 홀스타인(Holstein) 우유보다 고형분 함량이 높은 것으로 보고되었다. 이 연구는 저지(Jersey) 와 홀스타인(Holstein) 우유의 가우다 치즈(Gouda cheese)가 만성 스트레스(CUMS, chronic unpredictable mild stress)에 미치는 영향을 조사했다. 치즈를 먹인 만성 스트레스 마우스 모델의 개선적 변화는 젖소 종에 관계없이 통계적으로 유의미하게 효과적으로 나타났다. 흥미롭게도 PCR을 통한 분변 미생물 균총 분석에서 저지 치즈를 섭취함으로써 Bacteroidetes가 증가하고 Firmicutes가 유의적으로 감소하는 것으로 나타났다. 종합하면, 본 연구는 치즈 섭취가 스트레스 개선 작용이 있음을 제시하며, 특히 장내 미생물 균총의 유익한 방향으로의 변화가 관찰되는데, 치즈의 생리활성물질 혹은 장내미생물 균총의 대사물질들이 이러한 행동·정신학적 개선 작용과의 연관성이 있음을 시사한다.

• Journal of Life Science
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• v.31 no.11
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• pp.995-1003
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• 2021

Chromatin remodeling regulates gene expression through epigenetic mechanisms. Aberrations in histone modification have been associated with depression-like behaviors in animal models. Additionally, growing evidence also indicates that epigenetic modification is associated with depression. p11 (S100A10) has been implicated in the pathophysiology of depression both in human and rodent models. In the present study, we investigated alterations in histone acetylation and methylation at the promoter of the p11 gene in the hippocampus of mice subjected to chronic unpredictable stress (CUS). C57BL/6 mice were exposed to CUS daily for 3 weeks. Depression-like behaviors were measured with the forced swimming test (FST). The levels of hippocampal p11 expression were analyzed by quantitative real-time polymerase chain reaction (PCR) and Western blotting. The levels of acetylated and methylated histone H3 at the promoter of p11 were measured by chromatin immunoprecipitation followed by real-time PCR. CUS-exposed mice displayed depression-like behaviors with prolonged immobility in FST. CUS led to significant decreases in the expression of p11 at both protein and mRNA levels. Meanwhile, there was a decrease in histone H3 acetylation (Ac-H3) and H3-K4 trimethylation (H3K4met3) and an increase in H3-K27 trimethylation (H3K27met3) at the p11 promoter. These results indicate that chronic stress causes the epigenetic suppression of p11 expression in the hippocampus.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.27-41
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• 2004

This study was performed to evaluate the effects of Jowiseungchungtang and fluoxetine 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 5 weeks. These CMS-treated rats were stratified into Jowiseungchungtang group, fluoxetine group and vehicle group. And control rats were also stratified into other CMS-treated group. The change of the consumption of sucrose solution was measured, and open field test were performed to investigate the anti-depression effect of Jowiseungchungtang and fluoxetine. The results were as follows : 1. The consumption of sucrose solution was significantly reversed in Jowiseungchungtang-treated group at 7 week, but there was no significant change in other groups. 2. CMS schedule decreased body weight. Jowiseungchungtang group and fluoxetine group showed significant decrease of body weight after 6 weeks. 3. In open field test, Jowiseungchungtang group and fluoxetine group showed no significant change of exploratory activity.