• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.361-367
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• 2000

Cocaine functions as indirect dopamine and serotonin (5-hydroxytryptamine, 5HT) agonists and induces genomic and behavioral alterations in the striatum. Previously we demonstrated that ritanserin, a 5HT2/1C receptor antagonist, is not responsible for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum (see the previous paper in this issue). In this study, it was hypothesized that dopamine and 5HT2/1C receptors are required for cocaine-induced behavioral alterations and c-fos and zif268 mRNA expression. This hypothesis was addressed by infusing amperozide which antagonizes both 5HT2/1C and dopamine receptors and was analyzed using the quantitative in situ hybridization histochemistry in vivo. Systemic injection of amperozide (5 mg/kg, s.c.) significantly blocked increase in behavior, c-fos and zif268 mRNA expression induced by 15 mg/kg cocaine, i.p., in the dorsal striatum. These data suggest that dopamine and 5HT2/1C receptors are necessary for cocaine-induced behavioral alterations and immediate early gene expression in the dorsal striatum.

• Korean Journal of Biological Psychiatry
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• v.19 no.1
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• pp.17-28
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• 2012

The primary purpose of this review is to present an overview of relationship between human spontaneous eyeblinking and internal cognitive processes. The second purpose is to address the neural substrates of human eyeblinking based on recent studies focusing on the central dopaminergic system and to explore the significance of spontaneous eyeblinks in neuropsychiatric disorders. We reviewed recent and previous studies on eyeblink patterns under various cognitive tasks. We also reviewed neural substrates of eyeblinking, particularly based on the central dopaminergic system. This paper suggests that spontaneous eyeblinks are highly correlated with various cognitive processes and the activity of central dopaminergic system. Various neuropsychiatric disorders are related to the alteration of the occurrence of eyeblinking. Spontaneous eyeblinking is the unique human behavior that occurs regularly without conscious effort. It is known that the rate of eyeblinking is modulated by internal cognitive processes and dopamine-related neuropsychiatric disorders. Further research is required to how the temporal dynamics of spontaneous eyeblinking is correlated with the disease activity and progression.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.357-360
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• 2009

It is hypothesized that a number of environmental factors affect animals' behavior. Without controlling these variables, it is very hard for researchers to get not only reliable, but replicable data from various behavioral experiments testing animals' cognitive as well as emotional functions. For example, laboratory mice which had restricted environment showed different synaptic potentiation properties with wild mice (Zhao MG et al., 2009). While performing behavioral experiments, however, it is sometimes inevitable that the researcher changes the animals' environments, as by switching the cages in which experimental animals are housed and separating animals raised together into small experimental groups. In this study, we investigated the effect of environmental changes on mice's emotional behaviors by socially isolating them or reducing the size of their cage. We found that social isolation selectively increases the animals' levels of anxiety, while leaving depression-like behaviors unchanged. On the other hand, alteration of the housing dimensions affected neither their anxiety levels nor their depression-like behaviors. These results suggest that environmental variables may have a prominent impact on experimental animals' emotional behaviors and possibly their psychological states, leading to bias in the behavioral data produced from experiments.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.79-83
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• 2009

Exposure to early stressful adverse life events such as maternal and social separation plays an essential role in the development of the nervous system. Adolescent Sprague-Dawley rats that were separated on postnatal day 14 from their dam and litters (maternal social separation, MSS) showed hyperactivity and anxiolytic behavior in the open field test, elevated plus-maze test, and forced-swim test. Biologically, the number of astrocytes was significantly increased in the prefrontal cortex of MSS adolescent rats. The hyperactive and anxiolytic phenotype and biological alteration produced by this MSS protocol may provide a useful animal model for investigating the neurobiology of psychiatric disorders of childhood-onset diseases, such as attention deficient hyperactive disorder.

• Steel and Composite Structures
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• v.42 no.1
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• pp.59-74
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• 2022

This study introduces a general reliability-based, performance-based design framework to design frames regarding their uncertainties and user-defined design goals. The Iterative-R method extracted from the main framework can designate a proper R (i.e., response modification factor) satisfying the design goal regarding target reliability index and pre-defined probability of collapse. The proposed methodology is based on FEMA P-695 and can be used for all systems that FEMA P-695 applies. To exemplify the method, multiple three-dimensional, four-story steel special moment-resisting frames are considered. Closed-form relationships are fitted between frames' responses and the modeling parameters. Those fits are used to construct limit state functions to apply reliability analysis methods for design safety assessment and the selection of proper R. The frameworks' unique feature is to consider arbitrarily defined probability density functions of frames' modeling parameters with an insignificant analysis burden. This characteristic enables the alteration in those parameters' distributions to meet the design goal. Furthermore, with sensitivity analysis, the most impactful parameters are identifiable for possible improvements to meet the design goal. In the studied examples, it is revealed that a proper R for frames with different levels of uncertainties could be significantly different from suggested values in design codes, alarming the importance of considering the stochastic behavior of elements' nonlinear behavior.

• Toxicological Research
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• v.30 no.4
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• pp.267-276
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• 2014

Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.113-125
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• 2023

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.6
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• pp.337-344
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• 2016

Objectives: The purpose of this study was to evaluate the anti-cancer activity of cisplatin by studying its effects on cell viability and identifying the mechanisms underlying the induction of cell cycle arrest and apoptosis on oral squamous cell carcinoma (OSCC) cell lines with varying p53 mutation status. Materials and Methods: Three OSCC cell lines, YD-8 (p53 point mutation), YD-9 (p53 wild type), and YD-38 (p53 deletion) were used. To determine the cytotoxic effect of cisplatin, MTS assay was performed. The cell cycle alteration and apoptosis were analyzed using flow cytometry. Western blot analysis was used to detect the expression of cell cycle alteration- or apoptosis-related proteins as well as p53. Results: Cisplatin showed a time- and dose-dependent anti-proliferative effect in all cell lines. Cisplatin induced G2/M cell accumulation in the three cell lines after treatment with 0.5 and $1.0{\mu}g/mL$ of cisplatin for 48 hours. The proportion of annexin V-FITC-stained cells increased following treatment with cisplatin. The apoptotic proportion was lower in the YD-38 cell line than in the YD-9 or YD-8 cell lines. Also, immunoblotting analysis indicated that p53 and p21 were detected only in YD-8 and YD-9 cell lines after cisplatin treatment. Conclusion: In this study, cisplatin showed anti-cancer effects via G2/M phase arrest and apoptosis, with some difference among OSCC cell lines. The mutation status of p53 might have influenced the difference observed among cell lines. Further studies on p53 mutation status are needed to understand the biological behavior and characteristics of OSCCs and to establish appropriate treatment.

• Korean Journal of Biological Psychiatry
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• v.13 no.2
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• pp.95-102
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• 2006

Object : Nerve growth factor(NGF) is a protein involved in neuronal survival and plasticity in the central nervous system, which might play an important role in stress, depression and suicide. This study was performed to determine whether there is an alteration in plasma NGF concentrations in depressed patients with suicidal attempt. Methods : The subjects were 32 depressed patients who attempted suicide and admitted in emergency room. Forty-four hospitalized non-suicidal depressive patients and the 30 normal controls were closely matched with the suicidal group in terms of age and sex. Individuals in all 3 groups were evaluated independently by a semi-structured interview for the purpose of establishing a DSM-IV criteria diagnosis. The severity of depressive symptoms was evaluated using Hamilton depression rating scale(HDRS). The severity of the suicidal behavior was evaluated by Weisman and Worden's risk-rescue rating(RRR) system and the Lethality Suicide Attempt Rating Scale(LSARS). Plasma NGF level was measured by the enzyme linked immunosorbent assay(ELISA) method. Results : There were no statistically significant differences of the plasma NGF levels among groups. LSARS and RRR did not reveal any significant correlation with ${\beta}$-NGF level in suicidal depressive patients. Conclusion : This study do not support an association between ${\beta}$-NGF and suicidal depression. However it is necessary to investigate this association through other route such as postmortem brain.

• The Korean Journal of Food And Nutrition
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• v.33 no.3
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• pp.347-355
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• 2020

Cognitive impairment is considered to be key research topics in the field of neurodegenerative diseases and in understanding of learning and memory. In the present study, we investigated neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts in hydrogen peroxide-induced neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley^® (SD) rat in vivo. Apoptotic cell death in neuroblastic PC12 cell line was induced by hydrogen peroxide for 1 hour at 100 μM. However, mixture of SC and RF treatment prevented peroxide induced PC12 cell death with no neurotoxic effects. For in vivo experiment, the effect of SC and RF extracts on scopolamine-induced cognitive impairment in SD rat was evaluated by spontaneous alternation behavior in Y-Maze test. After 30 min scopolamine injection, the scopolamine-induced rats presented significantly decreased % spontaneous alteration and acetylcholine level, compared to non-induced group. However, treatment of SC+RF extracts rescued the reduced % spontaneous alteration with acetylcholine concentration from hippocampus in scopolamine-induced rats. These results suggested that mixture of SC and RF extract may be a potential natural therapeutic agent for the prevention of cognitive impairment.