• 생명과학회지
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• 제29권5호
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• pp.564-569
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• 2019

최근 알코올 소비량이 증가함에 따라 과량의 에탄올을 섭취하는 경우 또한 늘어나고 있다. 이런 과도한 에탄올 섭취는 ${\gamma}$-aminobutyric acid (GABA) 수용체의 활성화와 glutamate 수용체의 활성 억제를 통해 신경계를 교란시켜 단기 기억 형성을 방해 한다. 알코올에 의한 인지기능의 저하는 알코올성 black out을 유도할 수 있으며, 반복될 경우 알코올성 치매로 이어질 수 있기 때문에 black out을 예방하는 치료제의 개발이 필요하다. 따라서 본 연구자는 해당 연구를 통하여 Cassia obtusifolia seeds 에탄올 추출물(COE)이 가진 black out 예방제로써의 가능성을 평가하였다. 본 연구에서는 에탄올에 의해 유도된 기억 장애에 대한 COE의 효과를 확인하였다. 실험 동물의 기억력을 측정하기 위하여 수동 회피 실험과 Y자 미로 실험을 수행하였고, 마우스 해마 절편을 사용하여 에탄올이 기억의 형성과 관련하여 장기 강화(long term potentiation; LTP)에 어떠한 영향을 끼치는지 전기생리학을 통해 확인하였다. 또한 ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 수용체 길항제인 NBQX ($50{\mu}M$)를 사용하여 에탄올에 의한 인지기능 장애와 관련이 있다고 알려진 N-Methyl-D-aspartate (NMDA) 매개 field 흥분성 시냅스 후 전위를 측정하였다. 결과적으로, COE는 에탄올에 의한 기억력의 손상을 방지하였고, 해마 절편에서 에탄올에 의해 감소된 LTP와 NMDA 매개 흥분성 시냅스 후 전위를 대조군과 비슷한 수준까지 회복시켰다.

• 대한한의학회지
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• 제22권1호
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• pp.78-89
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• 2001

Objectives : The purpose of this investigation is to evaluate the effects of Woohwangcheongsim-won on reperfusion following MCA occlusion in rats. Methods : To evaluate the effect of Woohwangcheongsim-won on reperfusion following MCA occlusion, the volume of cerebral ischemia and edema were measured and the change of the CAI pyramidal neuron in the hippocampus was investigated by light microscopy. And the changes of several neurotransmitters and enzymes were investigated with the immunohistochemical methods. Results : 1. The volume of the control group, which was ischemic-damaged was 23.6%, and that of the sample group was 13.5%. 2. The voluminalratio of the right/left hemisphere was 116 in the control group, and that of the sample group was 107. 3. The pyramidal cells of CAI area in the control group were greatly damaged. The cells were changed into discontinuous and unsystematic forms, and nuclei, and cytoplasms were shrunk. On the other hand, the cells of the sample group were less damaged. 4. On the immunohistochemical methods, the sensitivities of GABA, NOS, DBH in the control group were increased, and those of synapsin and $eEF-l{\alpha}$ were decreased as compared with the normal group. NOS and DBH which were negative in the normal group showed positive reaction. On the other hand, the sensitivities of GABA, NOS and DBH in the sample group were decreased, but those of NPY, synapsin, CaMKII and $eEF-l{\alpha}$ were increased as compared with the control group. Conclusions : Woohwangcheongsim-won reduced the volume of cerebral ischemia and edema, and minimized the damage of pyramidal cells. The mechanism was related to protein synthesis, such as synapsin, ${\alpha}CaMKII$ and $eEF-l{\alpha}$, which resist neurotoxicity of glutamate receptors.

• 한국콘텐츠학회논문지
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• 제20권2호
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• pp.462-471
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• 2020

일반적으로 수면제로 사용되는 졸피뎀은 신경 억제 물질을 증가시키기 위해 GABA 수용체에 결합한다. 실제 졸피뎀을 4주 이상 연속으로 복용하는 경우는 많이 있다. 현재 한국에서 시행되고 있는 의약품 사용평가(DUR)은 졸피뎀의 사용 패턴을 확인할 수 있다. 수면제인 졸피뎀의 과다 사용을 예방 할 필요가 있다. 본 연구는 2019년 5월 10일부터 2019년 5월 15일까지 진행되었다. 검색된 총 125,197건의 문서 중 1차 및 2차 선별을 실시하여 진행하였다. 졸피뎀 과다 사용과 직접적인 관련이 있는 최종 254개의 문헌 사례를 선정하였다. 체계적인 문헌 연구를 통해 졸피뎀의 과다 사용을 예방 할 수 있는 방안을 모색하고자 하였다. 연구대상 선별과정에서 연구의 비뚤림 효과를 최소화 하였다. 졸피뎀의 과다 사용은 심각했으며 사용량이 계속 증가하는 추세였다. 졸피뎀을 이용한 범죄도 증가하고 있었다. 졸피뎀은 마약류 통합 관리 시스템과 의약품 사용평가를 통해 관리 될 수 있다고 연구되었다. 졸피뎀의 사용을 줄이기 위해서는 마약류 통합관리 시스템과 과다 사용자 교육을 통한 수요와 공급을 동시에 억제할 필요가 있다.

• Biomolecules & Therapeutics
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• 제15권3호
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• pp.175-181
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• 2007

Zizyphi Spinosi Semen (ZSS), a traditional Chinese folk medicine, has been used for treatment of insomnia and anxiety. This experiment was performed to investigate the anxiolytic-like effect of methanol extract of ZSS (MEZSS) in mice by using the experimental paradigms of anxiety and compared with that of a known anxiolytic, diazepam. In the elevated plus-maze test, it showed that MEZSS (100 mg/kg, p.o.) and diazepam (2.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries. MEZSS (50, 100 and 200 mg/kg, p.o.) and diazepam (0.5 mg/kg, p.o.) significantly increased the number of head dips compared with that of control group in the hole-board test. However, MEZSS has no effect on decreasing the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly inhibited locomotor activity. MEZSS did not decrease the strength force in the grip strength test, either. In addition, GABAergic involvements were also investigated to understand the possible mechanisms. $GABA_{A}$ receptors subunits and glutamic acid decarboxylase (GAD) were not over expressed, compared with that of the saline group. We also found that MEZSS did not increase chloride influx in cultured cerebellar granule cells. It is concluded that MEZSS might have anxiolytic-like effects, but these effects might not be mediated by GABAergic transmission.

• The Korean Journal of Pain
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• 제35권4호
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• pp.391-402
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• 2022

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.

• 생명과학회지
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• 제20권1호
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• pp.1-8
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• 2010

본 연구자들의 앞선 연구에서는 햄스터 상구에서 AMPA 수용체의 아형인 GluR1과 GluR4의 분포와 눈 적출 이후 이들 수용체의 분포를 면역세포화학적 방법으로 연구하였다. 또한, 표지한 GluR1과 GluR4를 칼슘결합단백질인 calbindin D28K, calretinin, parvalbumin과 GABA로 표지하여 비교하였다. 본 연구에서 역행성이동추적물질(retrograde tracer)인 호스래디시퍼옥시다아제(horseradish peroxidase, HRP)를 상구의 각 주요 상행로와 하행로에 주입함으로써 GluR1- 면역반응 신경세포들과 GluR4- 면역반응 신경세포들이 투사신경세포(projection neurons)임을 밝혀내었다. Tecto-reticulospinal pathway (TRS)와 dorsal lateral geniculate nucleus (dLGN)으로 HRP 를 주입한후, 햄스터들은 회복을 위해 48시간 동안 살려둔 뒤 관류(perfusion)하였다. GluR- 면역반응 처리된 절편들은 역행성 표지된 신경세포를 지님을 확인하였다. HRP를 주입하였더니 단지 적은 수의 GluR1- 면역반응 신경세포들이 TRS (1.4%)와 dLGN (2.6%)으로 투사되었고, 반면에 많은 수의 GluR4- 면역반응 신경세포들이 TRS (32.7%)로 투사되었다. 사이/투사 신경세포(inter/projection neurons)들은 GluR 아단위들의 분류된 분포와 차별화된 양상을 보였고 이들의 이러한 분포는 칼슘결합단백질들과 GABA와는 겹쳐지지 않았으며, 일전에 발표했던 시각적 행동 반응에서 안구 적출 후 수용체 아단위들의 기능적 다양화와는 차별화된 양상을 보였다.

• 생물정신의학
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• 제8권1호
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• pp.62-70
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• 2001

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.337-343
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• 2010

Long-term potentiation (LTP) and long-term depression (LTD) have both been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. In a previous study, we suggested that a developmental increase in serotonin [5-hydroxytryptamine (5-HT)] might be involved in the decline of LTP, since 5-HT inhibited its induction. In the present study, to further understand the role of 5-HT in a developmental decrease in plasticity, we investigated the effect of 5-HT on the induction of LTD in the pathway from layer 4 to layer 2/3. LTD was inhibited by 5-HT ($10{\mu}M$) in 5-week-old rats. The inhibitory effect was mediated by activation of 5-$HT_2$ receptors. Since 5-HT also regulates the development of visual cortical circuits, we also investigated the role of 5-HT on the development of inhibition. The development of inhibition was retarded by chronic (2 weeks) depletion of endogenous 5-HT in 5-week-old rats, in which LTD was reinstated. These results suggest that 5-HT regulates the induction of LTD directly via activation of 5-$HT_2$ receptors and indirectly by regulating cortical development. Thus, the present study provides significant insight into the roles of 5-HT on the development of visual cortical circuits and on the age-dependent decline of long-term synaptic plasticity.

• Biomolecules & Therapeutics
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• 제26권4호
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• pp.343-349
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• 2018

Although drugs such as barbiturates and benzodiazepines are often used for the treatment of insomnia, they are associated with various side effects such as habituations, tolerance and addiction. Alternatively, natural products with minimal unwanted effects have been preferred for the treatment of acute and/or mild insomnia, with additional benefits of overall health-promotion. Basic and clinical researches on the mechanisms of action of natural products have been carried out so far in insomnia treatments. Recent studies have been focusing on diverse chemical components available in natural products, with an interest of developing drugs that can improve sleep duration and quality. In the last 15 years, our co-workers have been actively looking for candidate substances from natural products that can relieve insomnia. This review is, therefore, intended to bring pharmacological data regarding to the effects of natural products on sleep duration and quality, mainly through the activation of $GABA_A$ receptors. It is imperative that phytochemicals will provide useful information during electroencephalography (EEG) analysis and serve as an alternative medications for insomnia patients who are reluctant to use conventional drugs.