• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.436-446
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• 2018

Background: The potential therapeutic values of Korean Red Ginseng extract (KRGE) in autoimmune disorders of nervous system have not been fully investigated. Methods: We used an acute experimental autoimmune encephalomyelitis animal model of multiple sclerosis and determined the effects and mechanism of KRGE on spinal myelination. Results: Pretreatment with KRGE (100 mg/kg, orally) for 10 days before immunization with myelin basic protein $(MBP)_{68-82}$ peptide exerted a protective effect against demyelination in the spinal cord, with inhibited recruitment and activation of immune cells including microglia, decreased mRNA expression of detrimental inflammatory mediators (interleukin-6, interferon-${\gamma}$, and cyclooxygenase-2), but increased mRNA expression of protective inflammatory mediators (insulin-like growth factor ${\beta}1$, transforming growth factor ${\beta}$, and vascular endothelial growth factor-1). These results were associated with significant downregulation of p38 mitogen-activated protein kinase and nuclear factor-${\kappa}B$ signaling pathways in microglia/macrophages, T cells, and astrocytes. Conclusion: Our findings suggest that KRGE alleviates spinal demyelination in acute experimental autoimmune encephalomyelitis through inhibiting the activation of the p38 mitogen-activated protein kinase/nuclear factor-${\kappa}B$ signaling pathway. Therefore, KRGE might be used as a new therapeutic for autoimmune disorders such as multiple sclerosis, although further investigation is needed.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.28-33
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant $GABA_A$ receptor (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, $Rb_1$, $Rb_2$, Rc, Rd, Re, Rf, $Rg_1$ and $Rg_2$, we found that Rc most potently enhanced the GABA-induced inward peak current ($I_{GABA}$). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the $GABA_A$ receptor. The effect of ginsenoside Rc on $I_{GABA}$ was both dose-dependent and reversible. The half-stimulatory concentration ($EC_{50}$) of ginsenoside Rc was 53.2$\pm$12.3 $\mu$M. Both bicuculline, a $GABA_A$ receptor antagonist, and picrotoxin, a $GABA_A$ channel blocker, blocked the stimulatory effect of ginsenoside Rc on $I_{GABA}$. Niflumic acid (NFA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), both $CI^{-1}$ channel blockers, attenuated the effect of ginsenoside Rc on I$I_{GABA}$. This study suggests that ginsenosides regulated $GABA_A$ receptor expressed in Xenopus oocytes and implies that this regulation might be one of the pharmacological actions of Panax ginseng.

• YAKHAK HOEJI
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• v.51 no.3
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• pp.219-227
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• 2007

Ginsenoside Rgl (Rgl), the pharmacologically active constituent of ginseng (Panax ginseng C.A. Meyer), has a variety of biological activities. The present study was undertaken to evaluate a possibility of Rgl whether it can be used in treatment or prevention of stress disorders. Animals were stressed by immobilization for 2 hours or electroshocks for 20 minutes. The normal group was not exposed to any stress. Rgl was subcutaneously injected as dosages of 5 and 10 mg/kg and red ginseng (RG) was orally administered 200 mg/kg as the positive control. Animals were given supplements for 5 days without stress, and then were given supplements for 5 days with stress. We recorded stress-related behavioral changes of experimental animals using the Etho-vision system. Weight of adrenal gland and levels of corticosterone in plasma were measured and stress related behaviors (smelling, grooming, face washing, rearing) were observed. Rgl didn't make significant behavioral changes in total open field and elevated plus maze test. Rgl did not influence on behavioral changes induced by electroshock stress. Whereas, 10 mg/kg of Rgl alleviated the increment of the freezing and face washing time and the decrement of the smelling and rearing time induced by restraint stress. The administration of Rgl 10 mg/kg has significantly increased the endurance time on rotating rod and swimming pool tests compared to the control group. These results indicate that Rgl can alleviate the damage induced by physical stress. This result suggests that Rgl may bea new candidate for treating stress related disorder.

• Genomics & Informatics
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• v.2 no.2
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• pp.81-85
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• 2004

To examine whether the IL-1A (-889) polymorphism associates with a risk for Alzheimer's disease (AD) and acts interactively with the apolipoprotein (APOE) $\epsilon$4 in the development of AD, we performed genotype analyses of the IL-1A and the APOE of the 102 Korean AD patients and 200 Korean non-demented controls. We failed to detect a significant difference in genotypic and allelic frequencies of IL-1A between the AD group and control group. No overexpression of the IL-1A C/T genotype and IL-1A T allele was found when we analyzed the late-onset and early-onset patients, separately. There was no significant genetic interaction between IL-1A polymorphism and the APOE polymorphism. I n conclusion, the IL-1A polymorphism did not contribute to the development of AD independently or interactively with the APOE $\epsilon$4 allele in Koreans.

• Journal of Digital Convergence
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• v.18 no.10
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• pp.137-146
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• 2020

The purpose of this study is to confirm the moderating effect of the 'IRrelevance Processing'(IRP) on the relationship between decision maker's openness and business problem solving creativity (BPSC). In order to confirm the psychological mechanism of BPSC and openness, we developed the irrelevance processing. In particular, the creativity in this study is different from the general creativity studied in psychology. BPSC is a study with practical value applied in the management environment. The results showed that openness of the decision maker was correlated with the BPSC, and that the irrelevance processing was a psychological mechanism to moderating effects relationship between openness of decision makers and BPSC. This paper proved the correlation between the propensity of decision makers and BPSC, and contributed to the study of corporate creativity by identifying the psychological mechanisms.

• Korean Journal of Biological Psychiatry
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• v.17 no.4
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• pp.203-209
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• 2010

Objectives : Increasing evidence suggests the presence of neurobiological bases for temperamental characteristics in humans. Brain correlates of harm avoidance(HA) have been most extensively studied using functional and structural brain imaging methods due to its potential link with anxiety and depressive disorders. To date, however, we are not aware of any reports that have examined the potential relationship between HA levels and regional cortical thickness. The aim of the current study is to examine the cortical thickness which is associated with HA temperament in healthy young subjects. Methods : Twenty-eight young, healthy individuals(13 men and 15 women, mean age, $29.4{\pm}6.3$ years) were screened for eligibility and administered the Korean version of the Cloninger's Temperament and Character Inventory and underwent high-resolution structural magnetic resonance imaging scanning. Results : HA was associated with cortical thickness in the right superior frontal cortex and in the left parietal cortex, adjusted for age and sex and corrected for multiple comparisons using the permutation testing method. Conclusion : Individual temperamental differences in HA are associated with structural variations in specific areas of the brain. The fact that these brain regions are involved in top-down modulations of subcortical fear reactions adds functional significance to current findings.

• Investigative Magnetic Resonance Imaging
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• v.2 no.1
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• pp.50-57
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• 1998

MR acoustic sound or noise due to gradient pulsings has been one of the problems in MRI, both in patient scanning as well as in many areas of psychiatric and neuroscience research, such as brain fMRI. Especially in brain fMRI, sound noise is one of the serious noise sources which obscures the small signals obtainable from the subtle changes occurring in oxygenation status in the cortex and blood capillaries. Therfore, we have studied the effects of acoustic or sound noise arising in fMR imaging of the auditory, motor and visual cortices. The results show that the acoustical noise effects on motor and visual responses are opposite. That is, for the motor activity, it shows an increased total motor activation while for the visual stimulation, corresponding(visual) cortical activity has diminished substantially when the subject is exposed to a loud acoustic sound. Although the current observations are preliminary and require more experimental confirmation, it appears that the observed acoustic-noise effects on brain functions, such as in the motor and visual cortices, are new observations and could have significant consequences in data observation and interpretation in future fMRI studies.

• Investigative Magnetic Resonance Imaging
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• v.19 no.4
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• pp.212-217
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• 2015

Purpose: For a single time-point hyperpolarized $^{13}C$ magnetic resonance spectroscopy imaging (MRSI) of animal models, scan-time window after injecting substrates is critical in terms of signal-to-noise ratio (SNR) of downstream metabolites. Pre-scans of time-resolved magnetic resonance spectroscopy (MRS) can be performed to determine the scan-time window. In this study, based on two-site exchange model, protocol-specific simulation approaches were developed for $^{13}C$ MRSI and the optimal scan-time window was determined to maximize the SNR of downstream metabolites. Materials and Methods: The arterial input function and conversion rate constant from injected substrates (pyruvate) to downstream metabolite (lactate) were precalibrated, based on pre-scans of time-resolved MRS. MRSI was simulated using two-site exchange model with considerations of scan parameters of MRSI. Optimal scan-time window for mapping lactate was chosen from simulated lactate intensity maps. The performance was validated by multiple in vivo experiments of BALB/C nude mice with MDA-MB-231 breast tumor cells. As a comparison, MRSI were performed with other scan-time windows simply chosen from the lactate signal intensities of pre-scan time-resolved MRS. Results: The optimal scan timing for our animal models was determined by simulation, and was found to be 15 s after injection of the pyruvate. Compared to the simple approach, we observed that the lactate peak signal to noise ratio (PSNR) was increased by 230%. Conclusion: Optimal scan timing to measure downstream metabolites using hyperpolarized $^{13}C$ MRSI can be determined by the proposed protocol-specific simulation approaches.

• Investigative Magnetic Resonance Imaging
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• v.19 no.2
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• pp.67-75
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• 2015

Purpose: To investigate the value of image post-processing software (FreeSurfer, IBASPM [individual brain atlases using statistical parametric mapping software]) and inversion time (TI) in volumetric analyses of the hippocampus and to identify differences in comparison with manual tracing. Materials and Methods: Brain images from 12 normal adults were acquired using magnetization prepared rapid acquisition gradient echo (MPRAGE) with a slice thickness of 1.3 mm and TI of 800, 900, 1000, and 1100 ms. Hippocampal volumes were measured using FreeSurfer, IBASPM and manual tracing. Statistical differences were examined using correlation analyses accounting for spatial interpretations percent volume overlap and percent volume difference. Results: FreeSurfer revealed a maximum percent volume overlap and maximum percent volume difference at TI = 800 ms ($77.1{\pm}2.9%$) and TI = 1100 ms ($13.1{\pm}2.1%$), respectively. The respective values for IBASPM were TI = 1100 ms ($55.3{\pm}9.1%$) and TI = 800 ms ($43.1{\pm}10.7%$). FreeSurfer presented a higher correlation than IBASPM but it was not statistically significant. Conclusion: FreeSurfer performed better in volumetric determination than IBASPM. Given the subjective nature of manual tracing, automated image acquisition and analysis image is accurate and preferable.