• Molecules and Cells
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• v.40 no.7
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• pp.495-502
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• 2017

The $5-HT_6R$ has been considered as an attractive therapeutic target in the brain due to its exclusive expression in the brain. However, the mechanistic linkage between $5-HT_6Rs$ and brain functions remains poorly understood. Here, we examined the effects of $5-HT_6R$-mediated cell morphological changes using immunocytochemistry, Western blot, and live-cell imaging assays. Our results showed that the activation of $5-HT_6Rs$ caused morphological changes and increased cell surface area in HEK293 cells expressing $5-HT_6Rs$. Treatment with 5-HT specifically increased RhoA-GTP activity without affecting other Rho family proteins, such as Rac1 and Cdc42. Furthermore, live-cell imaging in hippocampal neurons revealed that activation of $5-HT_6Rs$ using a selective agonist, ST1936, increased the density and size of dendritic protrusions along with the activation of RhoA-GTP activity and that both effects were blocked by pretreatment with a selective $5-HT_6R$ antagonist, SB258585. Taken together, our results show that $5-HT_6R$ plays an important role in the regulation of cell morphology via a RhoA-dependent pathway in mammalian cell lines and primary neurons.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.15-20
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• 2015

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and ${\gamma}$-aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.

• Toxicological Research
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• v.25 no.1
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• pp.17-21
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• 2009

The effects of aqueous extract of Schizandra Chinensis Fruit (AESC) on cadmium-induced changes of monoamine neurotransmitters in the different brain regions of adult rats were investigated. Male rats were received intraperitoneal (i.p.) administration of CdCl2 (0.6 mg/kg/d) for 21 days and sacrificed 7 days after the last administration. Concentrations of norepinephrine (NE), dopamine (DA) in striatum and serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) in cortex were measured by HPLC. There were significant decreases of NE, DA, 5-HT and 5-HIAA in Cd intoxicated rats (P < 0.05), while pretreatment with AESC (20 mg/kg/d or 60 mg/kg/d, p.o., 30 min before $CdCl_2$) greatly inhibited the decrease of monoamine transmitters, respectively (P < 0.05). Also, AESC significantly increased the reduction of glutathione contents and superoxide dismutase activities in cortex induced by $CdCl_2$. These results suggest that AESC ameliorates Cd-induced depletion of monoamine neurotransmitters in brain through its antioxidant activity.

• Herbal Formula Science
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• v.12 no.2
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• pp.77-93
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• 2004

Depression is a sort of mental disorder which is very common. To treat depression, many drugs such as TCA, MAOI are developed and used. But they have a lot of side effects, so it needs to develop drugs without side effects or with less side effects. Herbal medicines have been used to treat diseases not only physical but also mental and have less side effects. therefore, it has been thoght the need to develop herbal medicine with antidepressant effect. The purpose of this study was to reseach antidepressant effect and influence on monoamines of chunwangboshimdan thought to have antidepressant according to ancient medical book- donguibogam- and recent reports. We used 'forced swimming test(FST)' to know antidepressant effect of chunwangboshimdan and HPLC to check the influence on monoamines and their metabolites(norepinephrine, dopamine, DOPAC, HVA, serotonin, 5-HIAA) of chunwangboshimdan after divided into cerebral cortex, striatum, hypothalamus and hippocampus. The results were obtained as follows: In the study of antidepressant effect by 'forced swimming test(FST)'method, chunwang boshimdan had a significant antidepressant effect. In the study of influence on monoamines by HPLC, chunwangboshimdan mainly increased dopamine among monoamines and their metabolites(norepinephrine, dopamine, DOPAC, HVA, serotonin, 5-HIAA) significantly in 4 parts of rat's brain above-mentioned. Calculated by turnover ratio formulae of monoamine, chunwangboshimdan has more results than Imipramine. These results suggest that chunwangboshimdan has antidepressant effect that is related with the increase of monoamines by suppressing their metabolism as its mechanism.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.282-291
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• 2020

Inhaled solvents such as toluene are of particular concern due to their abuse potential that is easily exposed to the environment. The inhalation of toluene causes various behavioral problems, but, the effect of short-term exposure of toluene on changes in emotional behaviors over time after exposure and the accompanying pathological characteristics have not been fully identified. Here, we evaluated the behavioral and neurochemical changes observed over time in mice that inhaled toluene. The mice were exposed to toluene for 30 min at a concentration of either 500 or 2,000 ppm. Toluene did not cause social or motor dysfunction in mice. However, increased anxiety-like behavior was detected in the short-term after exposure, and depression-like behavior appeared as delayed effects. The amount of striatal dopamine metabolites was significantly decreased by toluene, which continued to be seen for up to almost two weeks after inhalation. Additionally, an upregulation of serotonin 1A (5-HT_1A) receptor in the hippocampus and the substantia nigra, as well as reduced immunoreactivity of neurogenesis markers in the dentate gyrus, was observed in the mice after two weeks. These results suggest that toluene inhalation, even single exposure, mimics early anxiety-and delayed depression-like emotional disturbances, underpinned by pathological changes in the brain.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.65-70
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• 2012

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-weekold rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-$HT_2$ receptors, but not by the activation of either 5-$HT_{1A}$ or 5-$HT_3$ receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

• Perspectives in Nursing Science
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• v.2 no.1
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• pp.76-91
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• 2005

Stroke patients often develop post stroke sequelae when they survive. Post stroke fatigue and emotional disturbances including depression are common along with motor dysfunction. However, medical personnel have paid relatively little attention to emotional changes and the presence of fatigue following strokes. Post-stroke fatigue was common, occurring in 57% of the patients in our series. The post-stroke fatigue appears to be related to the pre-stroke fatigue, physical disability and post stroke depression (PSD) although the relation to the lesion location remains elusive. The prevalence of post-stroke emotional disturbance has been reported to range from 12% to 64%. The wide variation in the frequency of post stroke depression may be related to methodological heterogeneity in items such as the criteria for depression, the timing of assessment, and the study population. Emotional incontinence, which is characterized by inappropriate or excessive laughing or crying is also common. The incidence of and factor related to this post-stroke emotional incontinence (PSEI) also remains unclear. We reported that out-patients with single, unilateral stroke, 18% had PSD and 34% had PSEI. Although both PSD and PSEI were related to motor dysfunction and location (anterior vs. posterior cortex) of the lesion, the latter was a stronger determinant for PSD. PSEI was more closely associated with subcortical strokes than was PSD. Another manifestation of post stroke patients is the occurrence of post stroke anger proneness (PSAP). They may become easily irritated, impulsive, less generous, and prone to be angry or aggressive at others. We also have reported the PSAP which seems to be closely associated with the presence of PSEI. The lesion distribution appears to be also similar. Both PSEI and PSAP respond well to serotonin reuptake inhibitors suggesting that these symptomsmay be possibly related to the alteration of serotonin after brain injury. Likewise, PSAP also produces a great deal of frustration and embarrassment among patients and caregivers. In summary, emotional disturbances such as depression, emotional incontinence, anger-proneness and fatigue are fairly common but under-recognized sequelae of stroke. These emotional disturbances decrease the quality of life of the patients and caregivers, and may adversely affect the overall prognosis. Therefore, these problems must be appropriately recognized and alleviated. Finding strategies to relieve the symptoms is imperative by understanding the causative factors in individual patient.

• Korean Journal of Pharmacognosy
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• v.42 no.1
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• pp.32-37
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• 2011

The effects of herbal ethanol extract from Gynostemma pentaphyllum (GP extract) on chronic stress-induced anxiety in mice were investigated. The animals were treated with GP extracts (50 and 100 mg/kg/day, p.o.) for 21 days before exposure to electric footshock (EF; duration and interval 10 sec for 3 min, 2 mA) for chronic stress once a day. The ambulatory locomotor activity was reduced by chronic EF stress and it was recovered by 12.9-15.1% in GP extract-treated groups. The grip strength was also significantly decreased by chronic EF stress, however, the EF-stressed groups treated with GP extract increased grip strength from 13.9% to 56.8% compared to EF-stressed groups. In addition, the serum levels of corticosterone were significantly elevated by chronic EF stress to 197% of the control levels, which was reduced to 73.1% by treatment with GP extract (100 mg/kg). In contrast, the brain levels of dopamine and serotonin were reduced to 67.6% and 63.1% by chronic EF stress, which was recovered to 90% of the control levels by treatment with GP extract. These results indicate that GP extract shows the ameliorating effects on chronic EF stress-induced anxiety in mice and it can be developed as the promising anti-anxiety agent.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.71-78
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• 2009

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

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