• 약학회지
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• 제45권4호
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• pp.419-425
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• 2001

The neuronal cell death induced by excess glutamate (Glu) has been implicated in many acute and chronic neurodegenerative diseases including cerebral ischemia. Glu-induced elevation of intra-cellular $Ca^{2+}$ plays a critical role in the excitotoxicity, partly through the activation of a variety of $Ca^{2+}$ dependent enzymes. In the present study, we investigated the Glu-induced modulation of $Ca^{2+}$/calmodulin-dependent protein kinase IV (CaMK IV), a multifunctional enzyme abundantly present in the nuclei of neurons. The exposure of cultured rat cortical neurons to $100{\mu}$M Glu for 3 min dramatically increased CaMK IV activity up to 4.5-fold of the control-treated enzyme activity. The activation was very rapid, reaching peak at 3 min and then declined gradually. Under the same experimental conditions, time-dependent acute and delayed neuronal cell death was observed. Immunoblot analyses using specific antibodies showed that the expressions of CaMK IV and $CaMKK_{\alpha}$ were time-dependently modulated by Glu. Taken together, these results imply that the modulation of CaMK IV activity by Glu may be involved in the cascade of events resulting in neuronal cell death in cortical cultures.

• 대한한의학회지
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• 제39권3호
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• pp.1-16
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• 2018

Objectives: The purpose of this study was to investigate the effects of 56 herbal formulae covered by the National Health Insurance Corporation (NHIC) on dementia-related biomarkers and neuronal cell changes. Methods: The 56 herbal formulae were extracted with 70% ethanol at $100^{\circ}C$ for 2 h. The antioxidant properties was measured by radical scavenging assay using ABTS+ radical. The acetylcholinesterase (AChE) activity was tested by Ellman's assay and $amyloid-{\beta}$ ($A{\beta}$) aggregation was determined using fluorescence method. To estimate the inhibitory effects of herbal formulae on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Results: Among the 56 herbal formulae, Dangguiyukhwangtang, Banhasasimtang, Samhwangsasimtang, Cheongwiesan, Hwangryunhaedoktang, Banhabaekchulchunmatang, Jaeumganghwatang, Cheongseoikgitang, and Hoechunyanggyuksan has a significant inhibitory effects on acetylcholinesterase (AChE) activity. Doinseunggitang and Samhwangsasimtang exerted the effect on the inhibition of $amyloid-{\beta}$ ($A{\beta}$) aggregation. Additionally, 10 herbal formulae affected AChE and $A{\beta}$ aggregation revealed antioxidant activity as well as neuroprotective and anti-neuroinflammation effects in neuronal cell lines. Conclusions: 10 herbal formulae that have been shown to be effective against the major dementia markers have been shown to have antioxidant activity, neuronal cell protection and inhibition of brain inflammation. Further investigation of these herbal formulae will need to be validated in dementia animal models.

• 대한한의학회지
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• 제23권3호
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• pp.145-163
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• 2002

Objectives: The purpose of this investigation was to evaluate the effects of Woohwangcheongsim-won and to study the mechanism for neuronal death protection in hypoxia with Embryonic day 20 (E20) cortical cells of a rat (Sprague Dawley). Methods: E20 cortical cells were dissociated in neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Woohwangcheongsim-won was added to the culture media for 24 hrs or 72 hrs. On 17 DIV, cells were given a hypoxic shock and further incubated in normoxia for another three days. On 20 DIV, Woohwangcheongsim-won's effects for neuronal death protection were evaluated by LDH assay, propidium iodide stain and phospho-H2AX immunostain and the mechanisms were studied by Bcl-2, Bak, Bax, caspase family, PKCα, ca1pain I. Results & Conclusions : 1. This study indicated that Woohwangcheongsim-won's effects for neuronal death protection in hypoxia were confirmed by LDH assay, propidium iodide stain and phospho-H2AX immunostain in culture method of Embryonic day 20(E20) cortical neuroblasts. 2. Woohwangcheongsim-won's mechanisms for neuronal death protection in hypoxia are to reduce the membrane damage fraction, to restrain DNA truncate, to restrain inflow of cytochrome c into cellularity caused by Bak diminution, to reduce the caspase cascade intiator caspase-8 and the effector caspase-3, to reduce the calpain I activity and to increase PKCand its activity in the membrane fraction. (J Korean Oriental Moo 2002;23(3):145～163)

• 생약학회지
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• 제50권2호
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• pp.118-123
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• 2019

Glutamate acts as an important neurotransmitter in brain. However, high concentration of glutamate showed an excitatory neurotoxicity and resulted to neuronal cell death. Neuronal cell death is known for one of the reason of Alzheimer's disease, a neurodegenerative disease. We tried to find neuroprotective medicinal plants by neuroprotection activity against glutamate injured HT22 cells as a model system. In the course of bioscreening of various medicinal plants, Taraxacum platycarpum extract showed significant neuroprotective activity. We tried to elucidate mechanisms of neuroprotective activity. T. platycarpum extract reduced ROS and intracellular $Ca^{2+}$ concentration increased by glutamate induced neurotoxicity. In addition, mitochondrial membrane potential was restored to the control level. Also, glutathione level, glutathione reductase and glutathione peroxidase activity were increased by T. platycarpum extract treatment. These data suggested that T. platycarpum showed neuroprotective activity via antioxidative activity.

• 한국식생활문화학회지
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• 제32권6호
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• pp.583-588
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• 2017

This study examined the antioxidant and neuronal cell protective effects of the water and methanol extracts of Eugenia caryophyllata Thunb. The total polyphenol content was significantly higher in the methanol extract than in the water extract. The DPPH radical scavenging activity in the water extract was similar to Vit. C at a concentration of $100{\sim}200{\mu}g/mL$. The ABTS radical scavenging activity in the water and methanol extract was similar to Vit. C at a concentration of $800{\sim}1,000{\mu}g/mL$. The superoxide dismutase (SOD)-like activity in the methanol extract was similar to Vit. C at a concentration of $800{\sim}1,000{\mu}g/mL$. The DPPH, ABTS radical scavenging and (SOD)-like activity increased with increasing extract concentration. In a cell viability using MTT, the water extract (50 and 100 ppm) and methanol extract (100 ppm) had a protective effect against $H_2O_2$-induced neurotoxicity.The result ssuggest that the extract of E. caryophyllata Thunb. has antioxidant activities and may be useful for treating neurodegenerative disorders.

• 응용통계연구
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• 제35권1호
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• pp.161-175
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• 2022

뇌활동으로 발생하는 전기신호는 다시 자기신호로 유도되는데 센서로 측정한 것을 뇌자도(magnetoencephalography, MEG)라고 한다. MEG 기술은 비접촉, 비침습적인 측정방법이고 시간분해능과 공간분해능력이이 우수하기 때문에 뇌의 기능적인 정보를 얻는데 유용하게 사용될 수 있다. 또한 MEG 신호를 측정하고 분석하여 뇌신경전류의 활동을 이해할 수 있고 나아가 정밀한 뇌기능 연구가 가능하다. 본 연구에서는 뇌 활동(brain activity) 현상에 관한 궁극적 정보를 얻기위해 MEG 데이터의 특성을 설명하고 통계적 문제를 다루어 앞으로 뇌연구에 통계학의 필요성과 뇌정보학의 중요성을 강조하고자 한다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.299-306
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• 2013

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

• 한국식품영양과학회지
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• 제41권11호
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• pp.1487-1492
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• 2012

본 연구는 치콘 추출물의 항산화 효능을 확인하고자 물과 에탄올로 추출하였다. 치콘에 포함된 총 폴리페놀 함량을 측정한 결과, 에탄올 추출물($37.3{\pm}5.2$ mg/GAE/g extract)과 열수 추출물($36.3{\pm}1.0$ mg/GAE/g extract)이 유사한 총 폴리페놀 함량을 포함하고 있었으며, 총 플라보노이드 함량은 물 추출물이 $47.0{\pm}3.8$ mg CE/g extract 그리고 에탄올 추출물이 $53.9{\pm}5.1$ mg CE/g extract를 나타내었다. ABTS를 이용한 라디칼 소거활성, FRAP를 이용한 환원력을 통한 항산화 활성을 측정한 결과에서도 치콘 추출물이 항산화 효과를 나타내었다. 한편, 세포 독성을 살펴보기 위하여 신경세포를 이용하여 MTT assay를 수행한 결과, 세포의 생존율은 1.0 mg/mL의 농도 이상에서는 생존에 영향을 미치지 않았고 신경세포 보호효능 실험에서는 2.5 mM의 $H_2O_2$로 유발시킨 산화적 손상에 대해 농도 의존적인 신경세포 보호 효과가 있었으며, 항산화 효소 활성을 SOD와 CAT로 분석한 결과 SOD는 0.5 mg/mL 농도에서 95% 이상의 활성과 CAT는 손상그룹에 비해 2배 이상의 활성을 각각 확인하였다. 또한 치콘 추출물이 세포사와 관련이 있는 단백질인 Bax와 Bcl-2의 발현을 조절하는 것을 확인하였다. 이와 같은 결과는 치콘 추출물이 산화적 손상의 억제를 통해 세포를 보호하는 효과가 있는 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.24-31
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• 2010

Taurine, 2-aminoethanesulfonic acid, is an abundant free amino acid present in brain cells and exerts many important biological functions such as anti-convulsant, modulation of neuronal excitability, regulation of learning and memory, anti-aggressiveness and anti-alcoholic effects. In the present study, we investigated to explore whether taurine has any protective actions against oxidative stress-induced damages in neuronal cells. ERK I/II regulates signaling pathways involved in nitric oxide (NO) and reactive oxygen species (ROS) production and plays a role in the regulation of cell growth, and apoptosis. We have found that taurine significantly inhibited AMPA induced cortical depolarization in the Grease Gap assays using rat cortical slices. Taurine also inhibited AMPA-induced neuronal cell damage in MTT assays in the differentiated SH-SY5Y cells. When the neuronal cells were treated with $H_2O_2$, levels of NO were increased; however, taurine pretreatment decreased the NO production induced by $H_2O_2$ to approximately normal levels. Interestingly, taurine treatment stimulated ERK I/II activity in the presence of AMPA or $H_2O_2$, suggesting the potential role of ERK I/II in the neuroprotection of taurine. Taken together, taurine has significant neuroprotective actions against AMPA or $H_2O_2$ induced damages in neuronal cells, possibly via activation of ERK I/II.

• 약학회지
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• 제46권3호
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• pp.185-191
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• 2002

Alzheimer's disease (AD) involves neuronal degeneration with impaired cholinergic transmission, particularly in areas of the brain associated with learning and memory. Several cholinesterase inhibitors are widely prescribed to ameliorate the cognitive deficits in AD patients. In an attempt to examine if tacrine and donepezil, two well-known cholinesterase inhibitors, exhibit additional pharmacological actions in primary cultured rat cortical cells, we investigated the effects on neuronal injuries induced by glutamate or N-methyl-D-aspartate (NMDA), $\beta$-amyloid fragment ( $A_{{beta}25-35)}$), and various oxidative insults. Both tacrine and donepezil did not significantly inhibit the excitotoxic neuronal damage induced by glutamate. However, tacrine inhibited the toxicity induced by NMDA in a concentration-dependent fashion. In addition, tacrine significantly inhibited the $A_{{beta}25-35)}$-induced neuronal injury at the concentration of 50 $\mu$M. In contrast, donepezil did not reduce the NMDA- nor $A_{{beta}25-35)}$-induced neuronal injury. Tacrine and donepezil had no effects on oxidative neuronal injuries in cultures nor on lipid peroxidation in vitro. These results suggest that, in addition to its anticholinesterase activity, the neuroprotective effects by tacrine against the NMDA- and $A_{{beta}25-35)$-induced toxicity may be beneficial for the treatment of AD. In contrast, the potent and selective inhibition of central acetylcholinesterase appears to be the major action mechanism of donepezil.