• Molecules and Cells
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• v.47 no.3
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• pp.100007.1-100007.11
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• 2024

Recent evidence establishes a pivotal role for obesity-induced inflammation in precipitating insulin resistance and type-2 diabetes. Central to this process is the proinflammatory M1 adipose-tissue macrophages (ATMs) in epididymal white adipose tissue (eWAT). Notably, natural killer (NK) cells are a crucial regulator of ATMs since their cytokines induce ATM recruitment and M1 polarization. The importance of NK cells is shown by the strong increase in NK-cell numbers in eWAT, and by studies showing that removing and expanding NK cells respectively improve and worsen obesity-induced insulin resistance. It has been suggested that NK cells are activated by unknown ligands on obesity-stressed adipocytes that bind to NKp46 (encoded by Ncr1), which is an activating NK-cell receptor. This was supported by a study showing that NKp46-knockout mice have improved obesity-induced inflammation/insulin resistance. We therefore planned to use the NKp46-knockout mice to further elucidate the molecular mechanism by which NKp46 mediates eWAT NK-cell activation in obesity. We confirmed that obesity increased eWAT NKp46⁺ NK-cell numbers and NKp46 expression in wild-type mice and that NKp46-knockout ablated these responses. Unexpectedly, however, NKp46-knockout mice demonstrated insulin resistance similar to wild-type mice, as shown by fasting blood glucose/insulin levels and glucose/insulin tolerance tests. Obesityinduced increases in eWAT ATM numbers and proinflammatory gene expression were also similar. Thus, contrary to previously published results, NKp46 does not regulate obesity-induced insulin resistance. It is therefore unclear whether NKp46 participates in the development of obesity-induced inflammation and insulin resistance. This should be considered when elucidating the obesity-mediated molecular mechanisms that activate NK cells.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.230-239
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• 2020

Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear. Here, the effects of imipramine on dendritic spine density and morphology in BLA and mPFC subregions of stressed mice were examined. Chronic restraint stress caused depressive-like behaviors such as enhanced social avoidance and despair level coincident with differential changes in dendritic spine structure. Chronic stress enhanced dendritic spine density in the lateral nucleus of BLA with no significant change in the basal nucleus of BLA, and altered the proportion of stubby or mushroom spines in both subregions. Conversely, in the apical and basal mPFC, chronic stress caused a significant reduction in spine density. The proportion of stubby or mushroom spines in these subregions overall reduced while the proportion of thin spines increased after repeated stress. Interestingly, most of these structural alterations by chronic stress were reversed by imipramine. In addition, structural changes caused by stress and blocking the changes by imipramine were corelated well with altered activation and expression of synaptic plasticity-promoting molecules such as phospho-CREB, phospho-CAMKII, and PSD-95. Collectively, our data suggest that imipramine modulates stress-induced changes in synaptic structure and synaptic plasticity-promoting molecules in a coordinated manner although structural and molecular alterations induced by stress are distinct in the BLA and mPFC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1585-1593
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• 2005

The genetic effects of restraint stress challenge on HPA axis and the therapeutic effect of Boshimgeonbi-tang on the stress were studied with cDNA microarray analyses, RT-PCR on hypothalamus using an immobilization-stress mice as an animal model. Male CD-1 mice were restrained in a tightly fitted and ventilated vinyl holder for 2hrs once a day, and this challenge was repeated for seven· consecutive days. In the change of body weight it showed that the Boshimgeonbi-tang is effected recovery on weight loss caused by the immobilization-stress. Seven days later, total RNA was extracted from the organs of the mouse, body-labeled with $CyDye^{TM}$ fluorescence dyes and then hybridized to CDNA microarray chip. Scanning and analyzing the array slides were carried out using GenePix4000 series scanner and GenePix $Pro^{TM}$ analyzing program, respectively. The expression profiles of 109 genes out of 6000 genes on the chip were significantly modulated in hypothalamus by the immobilization stress. Energy metabolism-, lipid metabolism-, apoptosis-, stress protein, transcriptional factor, and signal transduction-related genes were transcriptionally activated whereas DNA repair-, protein biosysthesis-, and structure integrity-related genes were down-regulated in hypothalamus. The 58 genes were up-regulated by the mRNA expression folds of 1.5 to 7.9. and the 51 genes were down-regulated by 1.5 - 5.5 fold. The 11 genes among them were selected to confirm the expression profiles by RT-PCR. The mRNA expression levels of Tnfrsf1a (apoptosis), Calm2 (cell cycle), Bag3 (apoptosis), Ogg1 (DNA repair), Aatk (apoptosis), Dffa (apoptosis), Fkbp5 (protein folding) were restored to the normal one by the treatment of Boshimgeonbi-tang.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1393-1403
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• 2003

The genetic effects of restraint stress challenge on HPA axis and the therapeutic effect of Boshimgeonbi-Tang on the stress were studied with cDNA microarray analyses on hypothalamus using an immobilization-stress mouse as stress model. Male CD-1 mice were restrained in a tightly fitted and ventilated vinyl holder for 2hours once a day, and this challenge was repeated for seven consecutive days. The body weights of the immobilization-stress mice were diminished about 25 percent degree as compared to normal ones. Seven days later, total RNA was extracted from the organs of the mouse, body-labeled with CyDye/sup TM/ fluorescence dyes (Amersham Bioscience Co., NJ), and then hybridized to cDNA microarray chip. Scanning and analyzing the array slides were carried out using GenePix 4000 series scanner and GenePix Pro/sup TM/ analyzing program, respectively. The expression profiles of 109 genes out of 6000 genes on the chip were significantly modulated in hypothalamus by the immobilization stress. Energy metabolism-, lipid metabolism-, apoptosis- and signal transduction-related genes were transcriptionally activated whereas DNA repair-, protein biosynthesis-, and structure integrity-related genes were down-regulated in hypothalamus. The 58 genes were up-regulated by the mRNA expression folds of 1.5 to 7.9. and the 51 genes were down-regulated by 1.5 - 3.5 fold. The 20 genes among them were selected to confirm the expression profiles by RT-PCR. The mRNA expression levels of Tnfrsf1a (apoptosis), Calm2 (cell cycle), Bag3 (apoptosis), Hspe1 (protein folding), Aatk (apoptosis), Dffa (apoptosis), Itgb1 (cell adhesion), Vcam1 (cell adhesion), Fkbp5 (protein folding), BDNF (neuron survival) were restored to the normal one by the treatment of Boshimgeonbi-Tang.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.118-125
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• 2008

Gardenia jasminoides (G. jasminoides) is traditionally used to treat insomnia, jaundice, emotional disorders, hepatic disease, and inflammatory disease. Previously, we found that geniposide and the water extract of G. jasminoides increased $Cl^-$ influx in neuroblastoma. Here we examined the sychopharmacological activities of G. jasminoides and its constituents. G. jasminoides extract was orally administered at 100 and 200 mg/kg, and genipin and geniposide were intraperitoneally injected at 2, 10, and 20 mg/kg. G. jasminoides extract (200 mg/kg) significantly decreased total open field activity but increased rearing activity in the center of the open field, suggesting an increase in exploratory activity. Genipin and geniposide did not change open field activity, but geniposide (20 mg/kg) increased rearing activity in the central area. The extract (200 mg/kg) significantly decreased rotarod and wire-balancing activity, but genipin and geniposide did not. No compounds influenced thiopental-induced sleeping or electroshock-induced seizures. The extract (200 mg/kg) significantly increased staying time in the open arms of the elevated plus maze and the entry ratio into the open arms, and geniposide (20 mg/kg) also increased open arm entry. Electroshock stress decreased open arm activity, but the extract and geniposide (20 mg/kg) significantly reversed that effect. This results indicate that G. jasminoides extract and geniposide alleviated anxiety with greater efficacy in stressed animals than normal animals.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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• pp.13-21
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• 2019

[Purpose] Chronic stress is a precipitating factor for depression, whereas exercise is beneficial for both the mood and cognitive process. The current study demonstrates the anti-depressive effects of regular exercise and the mechanisms linked to hippocampal neurogenesis. [Methods] Mice were subjected to 14 consecutive days of restraint, followed by 3 weeks of treadmill running, and were then subjected to behavioral tests that included the forced swimming and Y-maze tests. Protein levels were assessed using western blot analysis and newborn cells were detected using 5-bromo-2'-deoxyuridine (BrdU). [Results] Three weeks of treadmill running ameliorated the behavioral depression caused by 14 days of continuous restraint stress. The exercise regimen enhanced BrdU-labeled cells and class III β-tubulin levels in the hippocampal dentate gyrus, as well as those of thioredoxin-1 (TRX-1) and synaptosomal β2-adrenergic receptors (β2-AR) under stress. In vitro experiments involving treatment with recombinant human TRX-1 (rhTRX-1) augmented the levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear β-catenin, and proliferating cell nuclear antigens, which were previously inhibited by U0216 and FH535 (inhibitors of ERK1/2 and β-catenin/T cell factor-mediated transcription, respectively). The hippocampal neurogenesis elicited by a 7-day exercise regimen was abolished by a selective inhibitor of β2-AR, butoxamine. [Conclusion] These results suggest that TRX-1-mediated hippocampal neurogenesis by β2-AR function is a potential mechanism underlying the psychotropic effect of exercise.

• The Journal of Internal Korean Medicine
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• v.23 no.1
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• pp.41-46
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• 2002

Background and Objectives ; This experimental study was conducted to evaluate an anti-stress effect of Gamisachi-tang(加味四七湯) on mice immobilized by stress. Methods : The experimental animals were immobilized by stress for 15 minutes, and administered 9mg/20g or 18mg/20g of Gamisachi-tang(加味四七湯) extract for seven days before they got stressed. The serotonin contents in the frontal cortex, hypothalamus, corpus striatum, hippocampus were measured by HPLC method in rat brain. Results : In frontal cortex, serotonin contents significantly decreased in both sample A and B group compared to the controlled group. In the hypothalamus, serotonin contents increased in both sample A and B group compared to the controlled group. In the corpus striatum, serotonin contents significantly increased in both sample A and B group compared to the controlled group. In the hippocamous, serotonin contents significantly increased in both sample A and B group compared to the controlled group. Conclusions : According to the above results, Gamisachi-tang(加味四七湯) had a significant impact on the changes in serotonin contents, which occurred in a separated part of mouse brain caused by stress.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.33 no.2
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• pp.124-128
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• 2000

This study was designed to investigate the effects of sea tangle(Laminaria japonica) extract (Dasi-Ex group: dry base $4.0{\%}$) and fucoidan-added (Fuco-I, II, III group: fucoidan of $1.0{\%}, 2.0{\%}, 3.0{\%}$ added to Dasi-EX) drinks on lipid metabolism of stressed mice. ICR male mice ($20 {\pm} 2 g$) were fed experimental diets and given free through water bottle filled with these beverages instead of water for 18 days including sociopsychological stress of 4 days. Dasi-Ex and Fuco-I, II, III groups resulted in slight decreases $3{\$}$ in body weight gain and $6{\~}12{\%}$ in feed and gross efficiencies compared with control groups. Serum protein contents were slightly increased $1{\~}5{\%}$ by administrations of these beverages compared with control group, reflecting inhibitory effect of sociopsychological stress by increase of protein levels. Significant differences in serum cholesterol contents of Dasi-Ex and Fuco-I groups could not be obtained, but Fuco-II and III groups resulted in marked decreases ($13{\~}17{\%}$) in serum cholesterol contents compared with control group. LDL-cholesterol contents resulted in marked decreases ($about 20 and 25{\%}$, respectively) in Fuco-II and III groups, whereas HDL-cholesterol content was significantly increases ($about 16{\%}$) in Fuco-III group compared with control group. Fuco-I, II and III groups resulted in a marked decreases ($15{\%}, 20{\%} and 40{\%}$, respectively) in atherogenic index (AI) compared with control group. Significant differences in serum lipid peroxide (LPO) contents of Dasi-Ex and Fuco-I groups could not be obtained, but Fuco-II and III groups resulted in a significant decrease about $10{\%}$ in serum LPO contents compared with control group. These results suggested that fucoidan drinks added sea tangle could significantly inhibited chronic degenerative diseases by improvement of effective lipid metabolism or fucoidan component.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.6
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• pp.764-769
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• 1999

This study was designed to investigate the effects of sea tangle (Laminaria japonica) extract (Dasi-Ex group: dry base $4.0\%$) and fucoidan-added (Fuco-I, II, III group: fucoidan of $1,0\%,\;2.0\%,\;3.0\%$ added to Dasi-Ex) drinks on the formation of oxygen radicals and scavenger enzyme activities of stressed mice. ICR male mice (20 $\pm$2 g) were fed experimental diets and these drinks instead of water for 18 days including 4 days of sociopsychological stress. Dasi-Ex and Fuco-I, II and III groups resulted in a marked decreases $20\~40\%$ in basal oxygen radical (BOR) formation, and $15\~25\%$ in induced oxygen radical (IOR) formation compared with control group. Hydroxyl radical formations were significantly inhibited about $10\%$ in Dasi-Ex group, while remarkably inhibited $30\~40\%$ in Fuco-I, II and III groups. lipid peroxide (ISO) levels in Dasi-Ex group were not significantly different from those of control group, tut Fuco-I, II and III groups resulted in a significant decreases about $10\%$ in LPO levels compared with control group, Dasi-Ex, Fuco-I, II and III groups resulted in a marked decreases ($31\%,\;36\%,\;39\%$ and $42\%$, respectively) in oxidized protein levels through production of carbonyl group. Significant differences in nitric oxide (NO) levels in Dasi-Ex group were not obtained, but NO levels were slightly inhibited about $7\%$ in Fuco-I and II groups and $20\%$ in Fuco-III group compared with control group. Significant differences in superoxide dismutase (SOD) and catalase (CAT) activities in Dasi-Ex and Fuco-I groups were not obtained, but Fuco-II and III groups resulted in a significant increases $25\~40\%$ in SOD activities, and about $10\%$ in CAT activities compared with control group. These results suggest that the sociopsychological stress and aging process could be effectively inhibited by biological activity of sea tangle and fucoidan components.