• Journal of Ginseng Research
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• 제39권2호
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• pp.148-154
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• 2015

Background: Ginseng is known to have antiapoptotic, anti-inflammatory, and antioxidant effects. The present study investigated a possible role of Korean Red Ginseng (KRG) in suppressing dopaminergic neuronal cell death and the cleavage of p35 to p25 in the substantia nigra (SN) and striatum (ST) using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Methods: Ten-week-old male C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 d, and then administered KRG (1 mg/kg, 10 mg/kg, or 100 mg/kg) once a day for 12 consecutive days from the first injection. Pole tests were performed to assess the motor function of the mice, dopaminergic neuronal survival in the SN and ST was evaluated using tyrosine hydroxylase-immunohistochemistry, and the expressions of cyclin-dependent kinase 5 (Cdk5), p35, and p25 in the SN and ST were measured using Western blotting. Results: MPTP administration caused behavioral impairment, dopaminergic neuronal death, increased Cdk5 and p25 expression, and decreased p35 expression in the nigrostriatal system of mice, whereas KRG dose-dependently alleviated these MPTP-induced changes. Conclusion: These results indicate that KRG can inhibit MPTP-induced dopaminergic neuronal death and suppress the cleavage of p35 to p25 in the SN and the ST, suggesting a possible role for KRG in the treatment of Parkinson's disease.

• BMB Reports
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• 제51권11호
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• pp.545-546
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• 2018

With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient's environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as $TGF-{\beta}$ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of $TGF-{\beta}1$ and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.166-171
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• 2007

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.85-91
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• 2019

Oxidative stress is considered a major contributor in the pathogenesis of diabetic neuropathy and in diabetes complications, such as nephropathy and cardiovascular diseases. Diabetic neuropathy, which is the most frequent complications of diabetes, affect sensory, motor, and autonomic nerves. This study aimed to investigate whether 7,8-dihydroxyflavone (7,8-DHF) protects SH-SY5Y neuronal cells against high glucose-induced toxicity. In the current study, we found that diabetic patients exhibited higher lipid peroxidation caused by oxidative stress than healthy subjects. 7,8-DHF exhibits superoxide anion and hydroxyl radical scavenging activities. High glucose-induced toxicity severely damaged SH-SY5Y neuronal cells, causing mitochondrial depolarization; however, 7,8-DHF recovered mitochondrial polarization. Furthermore, 7,8-DHF effectively modulated the expression of pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) under high glucose, thus inhibiting the activation of caspase signaling pathways. These results indicate that 7,8-DHF has antioxidant effects and protects cells from apoptotic cell death induced by high glucose. Thus, 7,8-DHF may be developed into a promising candidate for the treatment of diabetic neuropathy.

• Journal of Korean Biological Nursing Science
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• 제10권2호
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• pp.176-183
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• 2008

Purpose: The purpose of this study was to identify the effect of Environmental Enrichment (EE) on improvement of motor function in animal models of Parkinson's Disease. Methods: Male C57BL6 mice weighing 25-30 g, at the age of 12 wks were used in this study. The animals were injected MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin, 20 mg/kg in saline, i.p.) 4 times a day at every 2 hr, and raised in EE cage for 14 days. On day 14, after behavior test, all mice were sacrificed for immunohistochemistry. All values were expressed as means$\pm$S.E.M. Statistical significance was evaluated using a one way ANOVA followed by Sheffe test. Results: There was a significant difference between the experimental group and the control group in the behavior test. Also EE significantly reduced of TH positive cell loss in Substantia nigra pars compacta as compared to the result of MPTP treatment. Conclusion: Based on these findings, it is reasonable to assume that the environmental enrichment prevents dopaminergic neuronal loss and improves disarrangement of motor function and behavioral disability induced by MPTP.

• Toxicological Research
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• 제28권2호
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• pp.107-112
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• 2012

Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental pollutants. Recently, it is suggested that neurotoxic effects such as motor dysfunction and impairment in memory and learning have been associated with PCB exposure. However, structure relationship of PCB congeners with neurotoxic effects remains unknown. Since PKC signaling pathway is implicated in the modulation of motor behavior as well as learning and memory and the role of PKC are subspecies-specific, we attempted to study the effects of structurally distinct PCBs on the total PKC activity as well as subspecies of PKC in cerebellar granule cell culture model. Cells were exposed to 0, 25 and 50 ${\mu}M$ of PCB-126, PCB-169, PCB-114, PCB-157, PCB-52 and PCB-4 for 15 min. Cells were subsequently analyzed by [$^3H$] phorbol ester binding assay or immunoblotted against PKC-${\alpha}$ and -${\varepsilon}$ monoclonal antibodies. While non-dioxin-like-PCB (PCB-52 and PCB-4) induced a translocation of PKC-${\alpha}$ and -${\varepsilon}$ from cytosol to membrane fraction, dioxin-like PCBs (PCB-126, -169, -114, -157) had no effects. [$^3H$] Phorbol ester binding assay also revealed structure-dependent increase similar to translocation of PKC isozymes. While PCB-4 induced translocation of PKC-${\alpha}$ and -${\varepsilon}$ was inhibited by ROS inhibitor, the pattern of translocation was not affected in presence of AhR inhibitor. It is suggested that PCB-4-induced PKC activity may not be mediated via AhR-dependent pathway. Taken together, our findings suggest that chlorination of ortho-position in PCB may be a critical structural moiety associated with neurotoxic effects, which may be preferentially mediated via non-AhR-dependent pathway. Therefore, the present study may contribute to understanding the neurotoxic mechanism of PCBs as well as providing a basis for establishing a better neurotoxic assessment.

• BMB Reports
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• 제55권4호
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• pp.181-186
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• 2022

Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.154-161
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• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• 생명과학회지
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• 제22권3호
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• pp.293-297
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• 2012

분자 운동 단백질은 신경세포 내의 세포체에서 특정 목적지까지 소포를 이동시키는데 관여한다. 오징어의 거대 축삭은 간단한 제거조작으로 축삭을 분리 가능하기 때문에 신경세포내 물질이동기전 연구의 좋은 모텔로 활용 가능하다. 이전연구에서 오징어 거대축삭의 소포들은 미세소관을 따라 이동하는 키네신 항체에 의하여 운반됨이 확인되었다. 본 연구는 오징어 뇌에 존재하는 키네신들을 크로닝하고, 분리된 유전자의 분석을 행하기 위하여 키네신 운동 도메인에서 잘 보존된 아미노산 배열에 해당되는 영역에 DNA primer을 이용하여 새로운 6종류의 키네신을 분리하였다. 오징어의 키네신들과 생쥐의 키네신들의 motor 영역의 아미노산분석에서 보존된 영역이 존재하며, Maximum Parsimony (MP) 방법, Neighbor-Joining (NJ) 방법, Minimum Evolution (ME) 방법, 그리고 Maximum likelihood (ML) 방법을 기초로 한 계통분석에서 생쥐의 키네신과 높은 상동성을 나타내었으며, 또한 계통수에서도 높은 상관관계가 확인되었다.

• 대한간호학회지
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• 제41권2호
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• pp.197-203
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• 2011

Purpose: This study was done to identify whether pre-conditioning exercise has neuroprotective effects against cerebral ischemia, through enhance brain microvascular integrity. Methods: Adult male Sprague-Dawley rats were randomly divided into four groups: 1) Normal (n=10); 2) Exercise (n=10); 3) Middle cerebral artery occlusion (MCAo), n=10); 4) Exercise+MCAo (n= 10). Both exercise groups ran on a treadmill at a speed of 15 m/min, 30 min/day for 4 weeks, then, MCAo was performed for 90 min. Brain infarction was measured by Nissl staining. Examination of the remaining neuronal cell after MCAo, and microvascular protein expression on the motor cortex, showed the expression of Neuronal Nuclei (NeuN), Vascular endothelial growth factor (VEGF) & laminin. Results: After 48 hr of MCAo, the infarct volume was significantly reduced in the Ex+MCAo group ($15.6{\pm}2.7%$) compared to the MCAo group ($44.9{\pm}3.8%$) (p<.05), and many neuronal cells were detected in the Ex+ MCAo group ($70.8{\pm}3.9%$) compared to the MCAo group ($43.4{\pm}5.1%$) (p<.05). The immunoreactivity of laminin, as a marker of microvessels and Vascular endothelial growth factor (VEGF) were intensively increased in the Ex+MCAo group compared to the MCAo group. Conclusion: These findings suggest that the neuroprotective effects of exercise pre-conditioning reduce ischemic brain injury through strengthening the microvascular integrity after cerebral ischemia.