• Korean Journal of Biological Psychiatry
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• v.17 no.4
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• pp.177-193
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• 2010

Significant advances have been made in understanding the biological underpinnings of post-traumatic stress disorder(PTSD), particularly in the field of genetics and neuroimaging. Association studies in candidate genes related with hypothalamic-pituitary-adrenal axis, monoamines including serotonin, dopamine and noradrenaline, and proteins including FK506-binding protein 5 and brain-derived neurotrophic factor have provided important insights with regard to the vulnerability factors in PTSD. Genome-wide association studies and epigenetic studies may provide further information for the role of genes in the pathophysiology of PTSD. Hippocampus, medial prefrontal cortex, anterior cingulated cortex and amygdala have been considered as key structures that underlie PTSD pathophysiology. Future research that combines genetic and neuroimaging information may provide an opportunity for a more comprehensive understanding of PTSD.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.1-6
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• 1990

We established an in vitro system of central serotonergic neurons by culturing dissociated rat embryonic (El4) brainstem cells to 14 days in vitro and monitored the serotonergic neuronal growth by measuring 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents in the cells with hish performance liquid chromatography with electrochemical detection (HPLC-EC). We studied also tile effects of various drugs on the contents of 5-HT and 5-HIAA, confirming in vivo reports. The 5-HT content (13 ng/mg protein) and 5-HT turnover rate (17 pmol/mg protein/h) at 14 days in vitro were in good agreement with those reported in the adult rat brain. The 5-HT content was more easily depleted with p-chlorophenylalanine, a tryptophan hydroxylase inhibitor than with NSD 1015 (3-hydroxybenzylhydrazine), an aromatic L-amino acid decarboxylase (AADC) inhibitor. Incubation of the cultures with tryptophan or 5-hydroxytryptophan increased the rate of serotonin formation implying that neither tryptophan hydroxylase nor AADC is saturated with its amino acid substrate in this in vitro system . The 5-HT content was depleted by reserpine. The 5-HT and 5-HIAA contents were increased and decreased, respectively, by monoamine oxidase inhibitors. All the above results indicate that the biochemical properties of the central serotonergic neurons in this culture system reflect reliably those of central serotonergic neurons in vivo. We suggest that measuring 5-HT and 5-HIAA contents in the primary cultured dissociated brainstem-cells with HPLC-EC is useful in the study of pharmacology as well as toxicolgy of the central serotonergic neurons.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.1
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• pp.32-37
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• 2017

Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tertrahydro-N-methyl-1-naphthalenamine (sertraline) hydrochloride from among selective serotonin reuptake inhibitors (SSRIs) is a treatment of major depression. For the differential diagnosis by metabolizing serotonin in a patient with neurological disorders, the radiolabeled $^{11}C$-sertraline was developed for non-invasive positron emission tomography in living brain and use the evaluation of new drug for SSRIs. We release the results of a fast and easy radiolabeling method applied a one-step loop method with $[^{11}C]CH_3OTf$ for routine clinical applications of $^{11}C$-sertraline. 1 mg of a precursor for $^{11}C$-sertraline in 0.1 mL DMF and $5{\mu}L$ of 1N NaOH, were injected into the loop of semi-prep high-performance liquid chromatography (HPLC). $[^{11}C]CH_3OTf$ was passed through the loop at room temperature (RT). The $^{11}C$-sertraline was separated by the semi-preparative HPLC. $^{11}C$-sertraline was eluted at 28.0 min was collected and evaluated by analytical HPLC and mass spectrometer. The total radiolabeling efficiency of $^{11}C$-sertraline was $30.7{\pm}8.7%$. The specific activity was $64.8{\pm}51.4GBq/{\mu}mol$. The radiochemical and chemical purities were higher than 99%. The mass spectrum of the product showed m/z peaks at 307.1 (M+1), indicating the mass of sertraline. By the one-step loop method with $[^{11}C]CH_3OTf$, $^{11}C$-sertraline could be quickly and easily prepared for clinical application.

• Korean Journal of Food Science and Technology
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• v.29 no.1
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• pp.156-160
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• 1997

The monoamine oxidase (MAO, EC 1.4.3.4) plays a central role in the metabolism of many amines including the neurotransmitter monoamines. MAO is a flavoprotein found exclusively in the mitochondrial outer membrane, occuring in the MAO-A and MAO-B subtypes. MAO-A deaminates serotonin and noradrenaline much better than phenethylamine (PEA) or benzylamine (BA), and is preferentially inhibited by clorgyline, whereas MAO-B prefers PEA and BA as substrates and is preferentially inhibited by deprenyl. MAO inhibitors were among the first drugs used in the treatment of depression, and it is known to be the inhibition of MAO-A which is important for the antidepressant effect of MAO inhibitors. For the purpose of evaluating MAO inhibitory activities from natural resources, three kinds of edible mushrooms were screened by tracing the inhibitory activities against rat brain mitochondrial MAO-A, utilizing serotonin as a substrate and rat liver mitochondrial MAO-B utilizing benzylamine as a substrate. Among the tested mushrooms, Ganoderma lucidium and Lentinus edodes showed the weak inhibitory activities against MAO-B.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.2
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• pp.117-127
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• 2002

Objective: This study was to investigate the generation of the functional neuron derived from human embryonic stem (hES, MB03) cells on in vitro neural cell differentiation system. Methods: For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for $7{\sim}10$ days, 20 ng/ml of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron, neural progenitor cells were cultured in i) N2 medium only (without bFGF), ii) N2 supplemented with 20 ng/ml platelet derived growth factor-bb (PDGF-bb) or iii) N2 supplemented with 5 ng/ml brain derived neurotrophic factor (BDNF) for 2 weeks. Identification of neural cell differentiation was carried out by immunocytochemistry using $\beta_{III}$-tubulin (1:250), MAP-2 (1:100) and GFAP (1:500). Also, generation of functional neuron was identified using anti-glutamate (Sigma, 1:1000), anti-GABA (Sigma, 1:1000), anti-serotonin (Sigma, 1:1000) and anti-tyrosine hydroxylase (Sigma, 1:1000). Results: In vitro neural cell differentiation, neurotrophic factors (PDGF and BDNF) treated cell groups were high expressed MAP-2 and GFAP than non-treated cell group. The highest expression pattern of MAP-2 and $\beta_{III}$-tubulin was indicated in BDNF treated group. Also, in the presence of PDGF-bb or BDNF, most of the neural cells derived from hES cells were differentiated into glutamate and GABA neuron in vitro. Furthermore, we confirmed that there were a few serotonin and tyrosine hydroxylase positive neuron in the same culture environment. Conclusion: This results suggested that the generation of functional neuron derived from hES cells was increased by addition of neurotrophic factors such as PDGF-bb or BDNF in b-FGF induced neural cell differentiation system and especially glutamate and GABA neurons were mainly produced in the system.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.99-110
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• 1985

Majarine that was isolated from Berberis Koreasra Palibin (Berberidaceae) is the isoquinoline alkaloid. The effects of dopaminergic and serotonergic antagonists on majarine induced changes in body temperature were studied in the mouse. Intraperitoneal administration of majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine caused a slight increase in body temperature. Majarine-induced hyperthermia was attenuated by the 5-HT antagonist, cyproheptadine However, it caused hyothermia in mice pretreated with the DA antagonist, haloperidol, and hyperthermia in mice pretreated with haloperidol and cyproheptadine in comparision with haloperidol pretreatment. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol and cyproheptadine, respectively. In reserpine pretreated mice, majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine pretreated with haloperidol caused no significant effect in body temperature. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol pretreatment in mice treated with reserpine and ${\alpha}$-methyl-p-tyrosine. These data suppose that both dopaminergic and serotonergic mechanisms in the brain mediate the effects of majarine on body temperature. We propose that majarine directly stimulate DA receptor, which secondarilly activate 5-HT neurons to cause changes in body temperature.

• Journal of Nutrition and Health
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• v.16 no.4
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• pp.243-252
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• 1983

This study was undertaken to invesigate the effect of early nutritional deprivation and environment on neurotransmitter concentrations and behavior in later life. The restoring process of rats fed foods ad libitum after 50% restriction of the casein or the Korean diet during the prenatal and/or the lactating periods was observed. There were two rearing conditions, isolated and enriched, after weaning. Behavioral development was measured by the Y- shaped water maze and the open field test. The neurotransmitters were analyzed after sacrifice at the age of 21 weeks. The results are summarized as follows. 1) The body weight impairment by dietary restriction during the prenatal and lactating periods could be restored within 18 weeks after weaning in case of living in a classical cage. The effect of quantitative restriction was bigger in the Korean diet than in the casein diet. 2) The brain weight was decreased by nutritional deprivation. Environmental enrichment increased it slightly. 3) The concentration of neurotransmitters, norepinephrine, dopamine, and serotonin, were not shown any traces of the dietary restriction at the age of 21 weeks. 4) In the maze test, the deprived rats made more errors than the nourished and the rats fed the Korean diet more than those fed the cascin dict. The environmental enrichment could decrease the number of errors. 5) In the open field test, the dietary deprived groups showed less reaction time, more squares entered in the field, and less number of fecal boli than the nourished among the environmentally isolated rats. However, rats living in the enriched cage without experience of nutritional stress showed the lowest emotionality and the elevated exploratory activity.

• The Korean Journal of Pain
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• v.25 no.4
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• pp.228-237
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• 2012

Background: Milnacipran is a balanced serotonin norepinephrine reuptake inhibitor with minimal side effects and broad safety margin. It acts primarily on the descending inhibitory pain pathway in brain and spinal cord. In many animal studies, intrathecal administration of milnacipran is effective in neuropathic pain management. However, there is no study for the neurological safety of milnacipran when it is administered neuraxially. This study examined the neurotoxicity of epidural milnacipran by observing behavioral and sensory-motor changes with histopathological examinations of spinal cords in rats. Methods: Sixty rats were divided into 3 groups, with each group receiving epidural administration of either 0.3 ml (3 mg) of milnacipran (group M, n = 20), 0.3 ml of 40% alcohol (group A, n = 20), or 0.3 ml of normal saline (group S, n = 20). Results: There were no abnormal changes in the behavioral, sensory-motor, or histopathological findings in all rats of groups M and S over a 3-week observation period, whereas all rats in group A had abnormal changes. Conclusions: Based on these findings, the direct epidural administration of milnacipran in rats did not present any evidence of neurotoxicity in behavioral, sensory-motor and histopathological evaluations.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.2
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• pp.88-96
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• 2020

Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) are herbal extracts widely used in food and traditional herbal medicine, and have the ability to perform a wide range of biological activities. We aimed to investigate the effects of the SH and VB combination (SHVB) on mice models of chronic restraint stress (CRS) and pentobarbital-induced sleeping behaviors to elucidate its possible mechanisms of action. CRS-exposed mice treated with SHVB showed significantly decreased immobility time, increased swimming and climbing times in the forced swim test (FST), and increased locomotor activity in the open field test (OFT). SHVB decreased serum CORT levels, but enhanced brain monoamine neurotransmitters. SHVB significantly decreased the sleep latency and increased total sleep duration in pentobarbital-induced sleeping behavior in mice. SHVB showed inhibitory effect on 5-HT_2A receptor-mediated ERK1/2 phosphorylation. These results suggest that SHVB has antidepressant and hypnotic effects by regulating the 5-HT_2A receptor.

• The Korea Journal of Herbology
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• v.30 no.3
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• pp.13-17
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• 2015

Objectives : Taraxacum platycarpum H. Dahlstedt has been reported to have several biological properties such as skin hydration and antiinflammation. The purpose of this study was to examine the antidepressive effects of water extract of T. platycarpum (WTP) on an animal model of depression. Methods : In the present study, normal ICR mice (4 weeks) were used, and orally administered with WTP (25, 50 and 100 mg/kg). Depression-like behavior was monitored the forced swimming test (FST) and tail suspension test (TST) in mice. The locomotor activity was evaluated to eliminate the false-positive activity in the open field test (OFT). Fluoxetine, the selective serotonin reuptake inhibitor, as a positive control was intraperitoneally administered at a dose of 15 mg/kg at 30 min before starting the behavioral test. Moreover, we evaluated the effects of WTP on the expression of brain-derived neurotrophic factor (BDNF) and the extracellular signal-regulated kinase (ERK)/ cyclic AMP response-element binding protein (CREB) signaling pathway in the hippocampus using Western blot. Results : The administration of WTP (50 and 100 mg/kg) significantly (P < 0.05, respectively) reduced the immobility time during FST and TST without accompanying changes in locomotor activity by OFT. Furthermore, WTP at dose of 100 mg/kg increased the BDNF expression and the phosphorylation of ERK and CREB in the hippocampus region. Conclusions : These results suggest that WTP has a useful anti-depressant effect through the regulation of BDNF/ERK/CREB signaling pathway.