• Journal of mucopolysaccharidosis and rare diseases
• /
• v.2 no.2
• /
• pp.43-45
• /
• 2016

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. Serotonin is among those traditional pharmacological targets for anti-obesity treatment because central 5-HT functions as an anorexigenic neurotransmitter in the brain. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Fat specific Tph1 knock-out (Tph1 FKO) mice exhibit similar phenotypes as mice with pharmacological inhibition of 5-HT synthesis, suggesting the localized effects of 5-HT in adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure in BAT and Htr2a KO mice exhibit the decreased lipid accumulation in WAT. These data suggest the clinical significance of the peripheral serotonergic system as a new therapeutic target for anti-obesity treatment.

• Journal of Ginseng Research
• /
• v.46 no.6
• /
• pp.819-829
• /
• 2022

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABA_A antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABA_A receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.6
• /
• pp.695-703
• /
• 1998

$[K^+]_o$ can be increased under a variety of conditions including subarachnoid hemorrhage. The increase of $[K^+]_o$ in the range of $5{\sim}15$ mM may affect tensions of blood vessels and can change their sensitivity to various vasoactive substances. Therefore, it was examined in the present study whether the sensitivity of cerebral arteries to vasoactive substances can be changed with the moderate increase of $[K^+]_o$, using Mulvany-type myograph and $[Ca^{2+}]_c$ measurement. The contractions of basilar artery and branch of middle cerebral artery induced by histamine were not increased with the elevation of $[K^+]_o$ from 6 mM to 9 mM or 12 mM. On the contrary, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$. The contractions were also significantly increased by the treatment with nitro-L-arginine $(10^{-4}$ M for 20 minutes). In the nitro-L-arginine treated arteries, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$ from 6 mM to 12 mM. $K^+-induced$ relaxation was evoked with the stepwise increment of extracellular $K^+$ from 0 or 2 mM to 12 mM by 2 mM in basilar arterial rings, which were contracted by histamine. But $[K^+]_o$ elevation from 4 or 6 mM to 12 mM by the stepwise increment evoked no significant relaxation. Basal tension of basilar artery was increased with $[K^+]_o$ elevation from 6 mM to 12 mM by 2 mM steps or by the treatment with ouabain and the increase of basal tension was blocked by verapamil. The cytosolic free $Ca^{2+}$ level was not increased by the single treatment with serotonin or with the elevation of $[K^+]_o$ from 4 mM to 8 or 12 mM. In contrast to the single treatment, the $Ca^{2+}$ level was increased by the combined treatment with serotonin and the elevation of $[K^+]_o$. The increase of free $Ca^{2+}$ concentration was blocked by the treatment with verapamil. These data suggest that the sensitivity of cerebral artery to serotonin is increased with the moderate increase of $[K^+]_o$ and the increased sensitivity to serotonin is due to the increased $[Ca^{2+}]_i$ induced by extracellular $Ca^{2+}$ influx.

• Journal of Aquaculture
• /
• v.9 no.4
• /
• pp.419-427
• /
• 1996

In order to obtain the basic information for seedling production of surf clam, Spisula sachalinensis, spawning induction and egg development were investigated. $NH_4OH$ addition and serotonin injection could induce the spawning in surf clam. Water temperature rising, sperm suspension immersion, UV-ray irradiated seawater and $H_2O_2$ addition less affected on induction of spawning than $NH_4OH$ and serotonin did. On the other hand, males were more sensitive to the treatments than females. The response time to initial spawning in the case of $NH_4OH$ addition was $3\~4$ hours. However in the case of serotonin injection, it was within 5 minutes. The number of eggs released by $NH_4OH$ addition were significantly more than those released by serotonin injection. The serotonin injection induced higher rates of germinal vesicle breakdown than the $NH_4OH$ addition. Fertilizing and hatching rates of the eggs also were the similar results. Eggs of surf clam were demersal isolated eggs and averaging $65.2{\pm}±1.8\;{\mu}m$ in diameter after spawning. Optimum range of water temperature for the development of egg was $15\~20^{\circ}C$, The required time for development of D-shaped larvae was 42 hours at $15^{\circ}C$ and 27 hours at $20^{\circ}C$, respectively.

• Journal of Life Science
• /
• v.20 no.10
• /
• pp.1451-1457
• /
• 2010

Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of cell-cell signaling in neuronal systems. The serotonin transporter (SERT) on the plasma membrane controls the extracellular 5-HT level by reuptake of released 5-HT from the synaptic cleft, but the underlying regulation mechanism is unclear. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of SERT and found a specific interaction with protein kinase C-$\varepsilon$ (PKC-$\varepsilon$), a PKC isotype that is characterized as a calcium-independent and phorbol ester/diacylglycerol-sensitive serine/threonine kinase. PKC-$\varepsilon$ bound to the tail region of SERT but not to other members of the $Na^+/Cl^-$ dependent SLC6 gene family in the yeast two-hybrid assay. The C-terminal region of PKC-$\varepsilon$ is essential for interaction with SERT. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. PKC-$\varepsilon$ phosphorylated the peptide of the SERT amino (N)-terminus in vitro. These results suggest that the phosphorylation of SERT by PKC-$\varepsilon$ may regulate SERT activity in plasma membrane.

• The Korean Journal of Zoology
• /
• v.33 no.3
• /
• pp.276-296
• /
• 1990

This study attempts to investigate several enteroendocrine cells in the gastrointestinal epithelia of the Korean snakes (Dinodon rufozonatum rufozonotum Rhabdophis tigrina tigrina, Enhydris rufodorsata, Agkistrodon blomhoffii brevicaudus, Agkistrodon saxatilis, Agkistodon calginosus). For a light-microscopical examination of immunocytochemistry, the paraffin sections (5 $\mu$ m) of tissue specimens taken from the various parts of the gastrointestinal tract were stained immunocytochemically by PAP procedure with 10 antisera. The frequency of enteroendocrine cells per unit area (mm$^2$) of each mucosa were counted and the shapes of the cells were observed. In Dinodon rufozonatum rufozonatum, Rhobdophis tigrina tigrina, Enhydris rufodorsata, Agkistrodon saxatilis and Agkistrodon caliginosus, cholecystokinin (CCK)-8, gastrin, pancreatic polypeptide (PP) and serotonin cells were observed. But the freuqency of these immunoreactive cells differ trom each portion of gastrointestinal tracts of all species, respectively. In Agkistrodon blomhoffii brevicaudus, CCK-8, gastrin and serotonin cells were observed. CCK-8 and serotonin cells were found in whole gastrointestinal tracts and gastrin cells were observed in pylorus and mucosa of small intestine. The frequency of these cells was different from each portion. The shapes of CCK-8, gastrin, PP and serotonin cells were pyramidal or oval and closed type in stomach. A large number of these cells were spindle in shape and open type in small intestine and anterior pant of large intestine, whereas some cells were closed type. In posterior part of large intestine and rectum, these cells were oval in shape and closed type.

• Korean Journal of Food Science and Technology
• /
• v.42 no.2
• /
• pp.142-146
• /
• 2010

Relatively large amounts of GABA can be produced by the fermentation of rice bran. Therefore, this study was conducted to investigate the effects of GABA on the secretion of melatonin and serotonin for the development of a sleep inductive compound. The secretion levels of melatonin and serotonin from mice were found to be $3.425{\pm}0.182\;pg/mL$ and $5.37{\pm}0.963\;ng/mL$, respectively, in response to feeding 120 mg/mL of GABA while they were $2.607{\pm}0.41\;pg/mL$ in the control. The secretion of both melatonin and serotonin was increased up to the 13.51% and 34.99%, respectively, when compared to the negative control. However, the feeding of milk alone did not have a great effect on the melatonin and serotonin secretions. Conversely, feeding of milk with GABA enhanced the secretion of serotonin. The amounts of both melatonin and serotonin secreted increased with respect to the increase in GABA concentrations during feeding. Interestingly, the induction level of melatonin was relatively higher than that of serotonin in response to feeding 120 mg/mL of GABA. This is the first study to report that GABA has an ability to induce sleep related hormones in mice; therefore, it has the potential for use as a natural sleep aid.

• 한국약용작물학회:학술대회논문집
• /
• 2008.11a
• /
• pp.306-307
• /
• 2008

• 대한핵의학회:학술대회논문집
• /
• 1966.11a
• /
• pp.96.4-97
• /
• 1966

• Journal of Life Science
• /
• v.20 no.6
• /
• pp.948-954
• /
• 2010

Exercise can favorably influence brain plasticity by facilitating neurogeneration, neuroadaptivity, and neuroprotection. Aerobic exercise has been reported to change brain nerve growth factors (growth hormone, insulin like factor-1, estrogen and serotonin). The purpose of this study was to demonstrate the effects of aerobic exercise for 12 weeks on brain nerve growth factors in girls. Fourteen female participants in elementary school grades 1 through 3 were randomly allocated to the exercise group (EG, n=6) and control group (CG, n=8). The EG participated in 60 minutes of modified ballet exercise as aerobic training three days a week for 12 weeks. Based on comparison between groups by two-way ANOVA with repeated measures, aerobic exercise program participants experienced decreased weight (p<0.01), BMI (p<0.01), fat mass (p<0.001), fat percent (p<0.001) and increased LBM (lean body mass) percent (p<0.001). In addition, we detected that aerobic exercise decreased the level of serotonin (p<0.05) and increased the level of GH (p<0.05) and IGF-1 (p<0.05). These findings suggest that aerobic exercise programs can be an efficient intervention to change body composition, alleviate central fatigue, improve brain function, and induce brain cell proliferation in girls.