• 대한전기학회논문지:시스템및제어부문D
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• 제55권2호
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• pp.45-51
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• 2006

In this paper, we propose a new architecture of Information Granulation based genetically optimized Self-Organizing Fuzzy Polynomial Neural Networks (IG_gSOFPNN) that is based on a genetically optimized multilayer perceptron with fuzzy polynomial neurons (FPNs) and discuss its comprehensive design methodology involving mechanisms of genetic optimization, especially information granulation and genetic algorithms. The proposed IG_gSOFPNN gives rise to a structurally optimized structure and comes with a substantial level of flexibility in comparison to the one we encounter in conventional SOFPNNs. The design procedure applied in the construction of each layer of a SOFPNN deals with its structural optimization involving the selection of preferred nodes (or FPNs) with specific local characteristics (such as the number of input variables, the order of the polynomial of the consequent part of fuzzy rules, and a collection of the specific subset of input variables) and addresses specific aspects of parametric optimization. In addition, the fuzzy rules used in the networks exploit the notion of information granules defined over system's variables and formed through the process of information granulation. That is, we determine the initial location (apexes) of membership functions and initial values of polynomial function being used in the premised and consequence part of the fuzzy rules respectively. This granulation is realized with the aid of the hard c-menas clustering method (HCM). To evaluate the performance of the IG_gSOFPNN, the model is experimented with using two time series data(gas furnace process and NOx process data).

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.283-289
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• 2019

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence- associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity. Tenovin-1-treated astrocytes showed increased SA-${\beta}$-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-$1{\beta}$, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.

• Journal of Ginseng Research
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• 제46권3호
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• pp.408-417
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• 2022

Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O₂ consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O₂ consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

• International Journal of Oral Biology
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• 제34권4호
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• pp.177-183
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• 2009

Human mesenchymal stem cell (hMSCs) isolated from human adult bone marrow have self-renewal capacity and can differentiate into multiple cell types in vitro and in vivo. A number of studies have now demonstrated that MSCs can differentiate into various neuronal populations. Due to their autologous characteristics, replacement therapy using MSCs is considered to be safe and does not involve immunological complications. The basic helix-loop-helix (bHLH) transcription factor Olig2 is necessary for the specification of both oligodendrocytes and motor neurons during vertebrate embryogenesis. To develop an efficient method for inducing neuronal differentiation from MSCs, we attempted to optimize the culture conditions and combination with Olig2 gene overexpression. We observed neuron-like morphological changes in the hMSCs under these induction conditions and examined neuronal marker expression in these cells by RTPCR and immunocytochemistry. Our data demonstrate that the combination of Olig2 overexpression and neuron-specific conditioned medium facilitates the neuronal differentiation of hMSCs in vitro. These results will advance the development of an efficient stem cell-mediated cell therapy for human neurodegenerative diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.281-285
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• 2012

A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubulea-ssociated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.

• 대한수의학회지
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• 제41권2호
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• pp.147-155
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• 2001

The immunocytochemical localization of tyrosine hydroxylase(TH) is examined in the developmental forebrain of mongolian gerbil in order to determine changes in the distribution and cytology of neurons. At each of the different developmental stage, including prenatal(E)14, E16, E18, E20, postnatal(P)0, P2, P4 days, mongolian gerbils were sacrificed. In E14, TH-IR cells were predominantly round or oval in shape and their processes were very short. In olfactory blub, TH-IR cells were begun to appear from E20. In the striatum, we observed only fibers of TH-IR at all ages. From E16, TH-IR perikarya and fiber were present in periventricular nucleus and paraventricular nucleus of hypothalamus. The changes from the early to the late prenatal stages of development appear to be the result of an increase in number of TH-IR perikarya and processes. These results were shown slight differences to other rodents.

• BMB Reports
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• 제54권6호
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• pp.311-316
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• 2021

Ethanol often causes critical health problems by altering the neuronal activities of the central and peripheral nerve systems. One of the cellular targets of ethanol is the plasma membrane proteins including ion channels and receptors. Recently, we reported that ethanol elevates membrane excitability in sympathetic neurons by inhibiting Kv7.2/7.3 channels in a cell type-specific manner. Even though our studies revealed that the inhibitory effects of ethanol on the Kv7.2/7.3 channel was diminished by the increase of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂), the molecular mechanism of ethanol on Kv7.2/7.3 channel inhibition remains unclear. By investigating the kinetics of Kv7.2/7.3 current in high K⁺ solution, we found that ethanol inhibited Kv7.2/7.3 channels through a mechanism distinct from that of tetraethylammonium (TEA) which enters into the pore and blocks the gate of the channels. Using a non-stationary noise analysis (NSNA), we demonstrated that the inhibitory effect of ethanol is the result of reduction of open probability (P_O) of the Kv7.2/7.3 channel, but not of a single channel current (i) or channel number (N). Finally, ethanol selectively facilitated the kinetics of Kv7.2 current suppression by voltage-sensing phosphatase (VSP)-induced PI(4,5)P₂ depletion, while it slowed down Kv7.2 current recovery from the VSP-induced inhibition. Together our results suggest that ethanol regulates neuronal activity through the reduction of open probability and PI(4,5)P₂ sensitivity of Kv7.2/7.3 channels.

• 대한수의학회지
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• 제48권3호
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• pp.251-258
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• 2008

The neurotoxicity of C-terminal fragments of amyloid precusor protein (CT) is known to play some roles in Alzheimer's disease progression. In this study, we investigated the effects of the recombinant C-terminal 105 amino acid fragment of amyloid precusor protein (CT105) on cholinergic function using CT105-injected rat. To study the effects of CT105 on septohippocampal pathway, choline acetyltransferase (ChAT) positive neurons were examined in the medial septum and in the diagonal band after an injection of CT105 peptide into the lateral ventricle. Immunohistological analysis revealed that the number of ChAT-immunopositive cells decreased significantly in both medial septum and diagonal band. In addition, CT105 decreased ChAT-immunopositive cells in the hippocampal area, particulary in the dentate gyros. To study the effect of amyloid beta peptide ($A{\beta}$) and CT105 on the cholinergic system, each peptide was injected into the left lateral ventricle, and acetylcholine (ACh) levels were monitored in hippocampus. ACh level in the hippocampal area was reduced to 60% of control level in $A{\beta}$-treated group, and the level was reduced to 15% of control level in CT105-treated group, at one week after the injection. ACh level was further reduced to 35% of control in $A{\beta}$-treated group, whereas the level was slightly increased to 30% of control in CT105-treated group at 4 weeks after the injection. Taken together, the results in the present study suggest that CT105 impairs the septohippocampal pathway by reducing acetylcholine synthesis and release, which results in damage of learning and memory.

• 대한수의학회지
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• 제57권1호
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• pp.1-7
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• 2017

Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is characterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6-OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDA-mediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion.

• 대한간호학회지
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• 제41권6호
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• pp.834-842
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• 2011

Purpose: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. Methods: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 ${\mu}g$) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. Results: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. Conclusion: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.