• Journal of Korean Neurosurgical Society
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• v.30 no.4
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• pp.417-424
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• 2001

Objective : Adrenal medullary chromaffin cells are known to release analgesic substances such as opioides and catecholamines. Transplantation of them is a novel method that challenges current approaches in treating chronic pain. The transplantation of xenogeneic chromaffin cells into the central nervous system(CNS) supply antinociception in animals. In this study, we investigated the analgesic effects of rat adrenal medullary chromaffin cells transplanted into the CNS of the mouse. To study the antinociceptive efficacy of transplanted chromaffin cells, the survival of rat adrenal medullary chromaffin cells transplanted into the CNS of mouse was determined. Methods : The adrenal medullary chromaffin cells isolated from rat were transplanted into the striatum of mouse. These cells were confirmed of the release of Met-enkephalin and Leu-enkephalin by HPLC, and immunoblots for tyrosine hydroxylase(TH). Two weeks after transplantation, we performed immunohistochemistry for TH to determine the survival of implanted cells and assessed pain sensitivity at the same time. Results : The isolated rat adrenal medullary chromaffin cells were positive for anti-TH antibody and released Met-enkephalin and Leu-enkephalin more than rat endothelial cells. Transplanted rat chromaffin cells were stained with anti-TH antibody in striatum of mouse after 2 weeks. Pain sensitivity was reduced on the chromaffin cell-transplanted mouse compared to endothelial cell-transplanted mouse by the hot plate test. Conclusion : These results suggest that the rat chromaffin cells were suitably transplanted into the CNS of mouse. This approach could be used as a therapy for reducing of chronic pain induced by cancer or neuronal injury.

• The Korea Journal of Herbology
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• v.30 no.2
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• pp.43-48
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• 2015

Objectives : The aim of this study was to investigate the memory enhancing properties of extract of Hoelen Cum Radix (HCR) and its possible mechanism in mice of normal condition. Methods : We evaluated the effects of HCR on cognitive function and memory enhancement in normal mice. Male ICR mice were orally administrated with HCR 100 mg/kg for 7 days and equal volume of saline was administrated to the control group in the same condition. We conducted two behavioral tests which measure the spatial working memory (Y-maze test) and cognitive fear memory (passive avoidance test). We also investigated whether HCR affects the hippocampal neurogenesis in the brain. To assess the effects of HCR on neural progenitor cell differentiation and neurite outgrowth in the early stage of hippocampal neurogenesis, we performed doublecortin (DCX), a direct neurogenesis marker, immunohistochemical analysis in the dentate gyrus (DG) of the mouse hippocampus. Results : HCR significantly enhanced memory and cognitive function as determined by the Y-maze test (p<0.05) and passive avoidance test (p<0.001). Moreover, HCR increased DCX positive cells (p<0.01) and neurite length (p<0.01) compared to the control group. These results indicated that HCR stimulates differentiation of neural progenitor cells and promotes neurite outgrowth in hippocampal DG of the mice. Conclusion : We concluded that HCR shows memory enhancing effects through the stimulation of hippocampal neurogenesis as a consequence of accelerated neuronal differentiation and neurite outgrowth in the DG of the hippocampus after HCR treatment.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.80-80
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• 2003

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by marked cell death in the striatum and cortex. Stereotaxic injection of quinolinic acid (QA) into striatum results in a degeneration of GABAergic neurons and exhibits abnormal motor behaviors typical of the illness. The objective of this study was carried out to obtain basic information about whether parthenogenetic mouse embryonic stem (PmES) cells are suitable for cell replacement therapy of HD. To establish PmES cell lines, hybrid F1 (C57BL/6xCBA/N) mouse oocytes were treated with 7% ethanol for 5 min and cytochalasin-B for 4 hr to initiate spontaneous cleavage. Thus established PmES cells were induced to differentiate using bFGF (20ng/ml) followed by selection of neuronal precursor cells for 8 days in N2 medium. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days, then a final differentiation step in N2 medium for 7 days. To establish recipient animal models of HD, young adult mice (7 weeks age ICR mice) were lesioned unilaterally with a stereotaxic injection of QA (60 nM) into the striatum and the rotational behavior of the animals was tested using apomorphine (0.1mg/kg, IP) 7 days after the induction of lesion. Animals rotating more than 120 turns per hour were selected and the differentiated PmES cells (1$\times$10$^4$cells/ul) were implanted into striatum. Four weeks after the graft, immunohistochemical studies revealed the presence of cells reactive to anti-NeuN antibody. However, only a slight improvement of motor behavior was observed. By Nissl staining, cell mass resembling tumor was found at the graft site and near cortex which may explain the slight behavioral improvement. Detailed experiment on cell viability, differentiation and migration explanted in vivo is currently being studied.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2018.10a
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• pp.448-451
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• 2018

The purpose of this study was to investigate the developmental process of myelination by neuron and Schwann cell cultures and the development of demyelination by herpes simplex virus-1 infection by electron microscopy and molecular biological analysis. The dorsal root ganglion (DRG) was isolated from the mouse embryo and Schwann cells and neuronal cells were cultured in vitro. Neuronal cells treated with mitotic inhibitors and purified Schwann cells were co-cultured together to induce myelination. The herpes simplex virus-1 was infected with the co-cultured cells, and the demyelination was induced. The myelin protein zero (MPZ) antibody, which means the presence of myelin formation, was used and electron microscopy was used to observe the development of myelin and dehydration.

• Korean Journal of Pharmacognosy
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• v.41 no.3
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• pp.190-195
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• 2010

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. NNMBS098, a composition comprising the water insoluble of the 70% EtOH extract of Zingiberis Rhizoma, showed the potent neuroprotective effects on glutamateinduced neurotoxicity by induced the expression of heme oxygenase (HO)-1 and increased HO activity in the mouse hippocampal HT22 cells. Furthermore, NNMBS098 caused the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in mouse hippocampal HT22 cells. In addition, we found that treatment with c-Jun N-terminal kinase (JNK) inhibitor (SP600125) reduced NNMBS098-induced HO-1 expression and NNMBS098 also increased JNK phosphorylation. Therefore, these results suggest that NNMBS098 increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through JNK pathway-Nrf2-dependent HO-1 expression.

• Molecules and Cells
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• v.21 no.1
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• pp.34-41
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• 2006

The neuronal localization of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor (GluR) subunits is vital as they play key roles in the regulation of calcium permeability. We have examined the distribution of the calcium permeable AMPA glutamate receptor subunit GluR1 in the mouse visual cortex immunocytochemically. We compared this distribution to that of the calcium-binding proteins calbindin D28K, calretinin, and parvalbumin, and of GABA. The highest density of GluR1-immunoreactive (IR) neurons was found in layers II/III. Enucleation appeared to have no effect on the distribution of GluR1-IR neurons. The labeled neurons varied in morphology; the majority were round or oval and no pyramidal cells were labeled by the antibody. Two-color immunofluorescence revealed that 26.27%, 10.65%, and 40.31% of the GluR1-IR cells also contained, respectively, calbindin D28K, calretinin, and parvalbumin. 20.74% of the GluR1-IR neurons also expressed GABA. These results indicate that many neurons that express calcium-permeable GluR1 also express calcium binding proteins. They also demonstrate that one fifth of the GluR1-IR neurons in the mouse visual cortex are GABAergic interneurons.

• Korean Journal of Pharmacognosy
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• v.53 no.2
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• pp.79-86
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• 2022

Excessive glutamate causes oxidative stress in neuronal cells, which can cause degenerative neurological disorders. We tried to find medicinal plant showed neuroprotective activity by using glutamate-injured HT22 cell as a model system. In this study, we found that Boesenbergia rotunda methanol extract showed neuroprotective activity against glutamate induced neurotoxicity in mouse hippocampal HT22 cells. B. rotunda methanol extract suppressed the formation of reactive oxygen species and decreased intracellular Ca²⁺concentration. Also, B. rotunda made mitochondrial membrane potential maintain to normal levels. In addition, B. rotunda increased total glutathione amount and activated antioxidative enzyme such as glutathione reductase and glutathione peroxidase compared to glutamate-treated groups. These results suggested that B. rotunda decreased neuronal cell death damaged by high concentrations of glutamate treatment, via antioxidative mechanism and might be one of candidate of development of new drug to treat neurodegenerative disease such as Alzheimer's disease.

• BMB Reports
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• v.56 no.5
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• pp.308-313
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• 2023

Phenotypic features such as ataxia and loss of motor function, which are characteristics of Parkinson's disease (PD), are expected to be very closely related to cerebellum function. However, few studies have reported the function of the cerebellum. Since the cerebellum, like the cerebrum, is known to undergo functional and morphological changes due to neuroinflammatory processes, elucidating key functional factors that regulate neuroinflammation in the cerebellum can be a beneficial therapeutic approach. Therefore, we employed PD patients and MPTP-induced PD mouse model to find cytokines involved in cerebellar neuroinflammation in PD and to examine changes in cell function by regulating related genes. Along with the establishment of a PD mouse model, abnormal shapes such as arrangement and number of Purkinje cells in the cerebellum were confirmed based on histological finding, consistent with those of cerebellums of PD patients. As a result of proteome profiling for neuroinflammation using PD mouse cerebellar tissues, fetuin-A, a type of cytokine, was found to be significantly reduced in Purkinje cells. To further elucidate the function of fetuin-A, neurons isolated from cerebellums of embryos (E18) were treated with fetuin-A siRNA. We uncovered that not only the population of neuronal cells, but also their morphological appearances were significantly different. In this study, we found a functional gene called fetuin-A in the PD model's cerebellum, which was closely related to the role of cerebellar Purkinje cells of mouse and human PD. In conclusion, morphological abnormalities of Purkinje cells in PD mice and patients have a close relationship with a decrease of fetuin-A, suggesting that diagnosis and treatment of cerebellar functions of PD patients might be possible through regulation of fetuin-A.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.389-396
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• 2001

Neuroprotective properties of lithium were investigated by using in vivo NMDA excitotoxicity model. The appearance of TUNEL positive cells was prominent within 24 h of NMDA (70 mg/kg, i.p.) injection in the regions of the cortex, hippocampal formation, and thalamus of mouse cerebrum. NMDA treatment resulted in the extensive enhancement of Bax immunoreactivity in the cortical and hippocampal regions. NMDA also increased the immunoreactivity of caspase 8 in the similar regions of the mouse cerebrum. However, the increased immunoreactivity of Bax and caspase 8 were dramatically attenuated by chronic lithium pretreatment (lithium chloride, 300 mg/kg/d, i.p. for $7{\sim}10$ days). At the same time, lithium ion blocked the appearance of TUNEL positive cells, and the morphological assessment indicated an effective neuroprotection by lithium against NMDA excitotoxicity. Although the exact action mechanism of lithium is not straightforward at this time, we propose that the inhibition of Bax and caspase cascade is involved in the neuroprotective action of lithium.

• Journal of Life Science
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• v.21 no.5
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• pp.647-655
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• 2011

The neurotoxicity of aggregated amyloid ${\beta}$ ($A{\beta}$) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase III inhibitor, on $A{\beta}_{25-35}$-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-${\gamma}$ activation. $A{\beta}_{25-35}$ significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from $A{\beta}$-induced cell death as well as rosiglitazone, a PPAR-${\gamma}$ activator. These effects were suppressed by GW9662, an antagonist of PPAR-${\gamma}$ activity, indicative of a PPAR-${\gamma}$-mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-${\gamma}$ activity levels that had been altered as a result of $A{\beta}_{25-35}$ treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of $A{\beta}_{25-35}$ in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 mg/kg) for 2 weeks before $A{\beta}_{25-35}$ injection and once a day for 4 weeks post-surgery almost completely prevented the $A{\beta}_{25-35}$-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate $A{\beta}_{25-35}$-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-${\gamma}$ activation. The phosphodiesterase III inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.