• BMB Reports
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• 제50권6호
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• pp.335-340
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• 2017

Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and $14-3-3{\zeta}$ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to $14-3-3{\zeta}$ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling.

• 생물정신의학
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• 제22권2호
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• pp.87-94
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• 2015

Objectives The power spectral analysis of electroencephalogram has been widely used to reveal the pathophysiology of the alcoholic brain. However, the results were not consistent and the three dimensional study can be hardly found. The purpose of this study was to investigate characteristics of the three dimensional electroencephalographic (EEG) activity of alcohol dependent patients using standardized low resolution electromagnetic tomography (sLORETA). Methods The participants consisted of 30 alcohol dependent patients and 30 normal healthy controls. All the participants were males who had refrained from alcohol at least one month and were not taking any medications. Thirty two channel EEG data was collected in the resting state with eyes-closed condition during 30 seconds. The three dimensional data was compared between two groups using sLORETA for delta, theta, alpha, beta1, beta2, and beta3 frequency bands. Results sLORETA revealed significantly increased brain cortical activity in alpha, beta1, beta2, and beta3 bands each in alcohol dependent patients compared to normal controls. The voxels showing the maximum significance were in the left transverse temporal gyrus, left superior temporal gyrus, left anterior cingulate, and left fusiform gyrus in alpha, beta1, beta2, and beta3 bands respectively. Conclusions These results suggest that chronic alcohol intake may cause neurophysiological changes in cerebral activity. Therefore, the measuring of EEG can be helpful in understanding the pathophysiology of cognitive impairements in alcohol dependence.

• Annals of Clinical Neurophysiology
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• 제1권1호
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• pp.10-18
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• 1999

연구배경 및 목적 : 시각 인지 과정은 영장류 실험을 통하여 다소 정보를 얻을 수 있었으나 인간에서는 아직 완전하게 이해되지 않고 있다. 이 연구의 목적은 뇌자극과 시가유발전위 검사를 토대로 인간의 시각피질의 기능적 분화와 시간 순으로 활성화되는 양상을 보고자 한 것이다. 연구방법 : 간질 수술을 위하여 후두엽과 인접 부위에 광범위하게 피질하전극을 넣은 22명의 환자를 대상으로 전기적 뇌자극과 시각유발전위 검사를 시행하였다. 뇌자극시 나타나는 반응은 형태, 색, 및 움직임의 세 가지로 크게 나누고 형태는 다시 단순, 중간 및 복잡한 형태로 세분하였다. 시각유발전위는 P1 혹은 IV파의 latency를 측정하였다. 결과 : 단순 혹은 중간 형태는 흔히 occipital pole과 striate cortex에서 발생하였다. 색반응은 후두엽의 기저부 즉, fusiform, lingual, inferior occipital gyri를 자극할 때 관찰되었다. 움직임 반응은 내측기저부 및 외측의 측후두엽 혹은 측두정후두부의 경계부에서 주로 나타났다. 결론 : 이러한 결과는 인간의 시각피질이 시각의 여러 가지 구성성분 즉, 형태, 색, 및 움직임에 대해서 각각 별도로 분화되어 있다는 것을 보여준다. 도한 시각자극이 전해지면 striate cortex와 occipital pole이 가장 먼저 활성화되고 이어서 내측 및 외측 후두엽 부위가 활성화된다는 것을 알 수 있다. 이러한 사실을 종합하여 보면 인간의 시각피질은 시각의 여러 구성성분별로 별도로 발달된 해부학적 경로를 통하여 각각의 기능에 대하여 특수하게 분화된 뇌세포에서 시각정보를 각각 분석하되 일정한 시간순서에 의한다는 것을 시사하는 것이다.

• 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.

• 대한통합의학회지
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• 제8권1호
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• pp.113-124
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• 2020

Purpose : The purpose of this study was to investigate the effects of exercise intervention combined with 3D visual feedback and motion observation on postural alignment and cerebral cortical activity in subjects with forward head posture (FHP). Methods : The study included 28 participants with FHP, randomly divided into a 3D visual feedback plus motion observation group (n=14) or control group (n=14). The experimental group received corrective exercise combined with 3D visual feedback and motion observation for FHP, three times a week for four weeks. We examined cervical spine radiographs in the lateral standing position with both arms crossed to measure the craniovertebral angle (CVA) and cervical lordosis (CL). Relative alpha (RA) and beta waves (RB) were measured by wireless dry EEG. Results : The CVA value was significantly different between the groups, and the CL value was significantly different only in the experimental group. RA and RB values were not significantly different before and after intervention in the control group. RB values were significantly decreased before and after intervention in the experimental group. Conclusion : Based on the results of this study, we suggest that interventions combined with motion observation and 3D visual feedback may be effective as exercise methods to improve postural alignment and cerebral activity in subjects with FHP. Further research is required to generalize our results on technical supplementation complemented with 3D visual feedback devices.

• 한국가축번식학회지
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• 제17권3호
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• pp.183-191
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• 1993

These experiments were carried out to investigate whether the enzyme is involved in zona hardening during normal activatin of the oocytes by sperm, and demonstrate peroxidase activity during in vitro fertilization of oocytes treated with peroxidase inhibitors(250 $\mu$M phenylhydrazine, 28mM sodium sulfite, 350mM glycine ethyl ester and 50mM sodium azide) and tyrosine analogue(12.5mM tyramine). Also, zona soluble properties of the ovarian oocytes incubated for 0, 5, 10 and 15 hr in the presence of pheylhydrazine or tyramine were studied by using $\alpha$-chymotrypsin. The results obtained from these experiments were summarized as follows ; 1. The rates of fertilizatin in control oocytes and oocytes treated with phenylhydrazine or tyramine were 69.8%, 62.3% and 88.2%, respectively. However in vitro fertilization in oocytes treated with three different peroxidase inhibitors, sodium sulfite, glycine ethyl ester and sodium azide, were not induced. The oocytes treated with phenylhydrazine had no significant effect on in vitro fertilization rate as compared to control. However there was a significantly different in fertilization between tyramine treated group and control group(P<0.01). 2. The zona solubility(t50) of control and fertilized oocytes in culture treated with phenylhydrazine or tyramine were 30.7, 26.0 and 16.3 min., respectively. Phenylhydrazine treated group and tyramine treated group had effect on inhibition of zona hardening as compared to control group. These results suggest that ovoperoxidase is involved in zona hardening during normal activation of the oocytes by sperm. 3. t50 of control oocytes and ovarian oocytes treated with phenylhydrazine or tyramine for 5, 10 and 15 hr in vitro were 14.0, 26.2 and 32.0 min., 14.5, 26.9 and 30.2 min., and 14.0, 24.3 and 31.2 min., respectively. These results suggest that zona hardening in ovarian oocytes matured for various times in vitro cannot be inhibited by peroxidase inhibitors and tyrosine analogue, that the spontaneous zona hardening incultured ovarian oocytes is not caused by the secretory products of cortical granules released during the cortical reaction, ovoperoxidase.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2004년도 International Meeting of the Microbiological Society of Korea
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• pp.141-146
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• 2004

SPIN90 was identified to farm molecular complex with $\betaPIX$, WASP and Nck. This complex shows that SPIN90 interacts with Nck in a manner dependent upon cell adhesion to extracellular matrix, but $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex was stable even in suspended cells. This suggests that SPIN90 serves as an adaptor molecule to recruit other proteins to Nck at focal adhesions. SPIN90 was phosphorylated by ERK1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of SPIN90 likely promotes the interaction of the $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex and Nck. It thus appears that the interaction of the $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex with Nck is crucial for stable cell adhesion and can be dynamically modulated by SPIN90 phosphorylation that is dependent on cell adhesion and ERX activation. SPIN90 directly binds syndapin I, syndapin isoform II-1 and II-s via its PRD region in vitro, in vivo and also associates with endocytosis core components such as clathrin and dynamin. In neuron and fibroblast, SPIN90 colocalizes with syndapins as puntate form, consistent with a role for SPIN90 in clathrin-mediated endocytosis pathway. Overexpression of SPIN90 N-term inhibits receptor-mediated endocytosis. Interestingly, SPIN90 PRD, binding interface of syndapin, significantly blocks internalization of transferrin, demonstrating SPIN90 involvement in endocytosis in vivo by interacting syndapin. Depletion of endogenous SPIN90 by introducing $\alpha-SPIN90$ also blocks receptor-mediated endocytosis. Actin polymerization could generate farce facilitating the pinch-out event in endocytosis, detach newly formed endocytic vesicle from the plasma membrane or push out them via the cytosol on actin tails. Here we found that SPIN90 localizes to high actin turn over cortical area, actin-membrane interface and membrane ruffle in PDGF treated cells. Overexpression of SPIN90 has an effect on cortical actin rearrangement as filopodia induction and it is mediated by the Arp2/3 complex at cell periphery. Consistent with a role in actin organization, CFP-SPIN90 present in actin comet tail generated by PIP5 $kinase\gamma$ overexpression. Therefore this study suggests that SPIN90 is functional linker between endocytosis and actin cytoskeleton.

• 생물정신의학
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• 제7권2호
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• pp.174-179
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• 2000

연구목적 : 환청이 자기감시체계의 이상이라고 주장하는 일부 학자들은 청각적 언어상상과 관련된 뇌 활성화 소견을 이용하여 환청의 병리기전을 밝히고자 하였다. 그런데 대부분의 환청의 내용은 부정적 감정을 동반하는 내용이다. 이런 점에서 저자들은 부정적 감정이 청각적 언어상상에 의해 유발된 대뇌 피질 활성에 어떤 식으로 영향을 미치는지 알아보고, 이를 통해 부정적 감정이 환청발생에 미칠 수 있는 영향을 이해해 보고자 하였다. 방법 : 정상인과 정신분열병 환자를 대상으로 부정적 내용의 청각적 언어상상 과제와 부정적 내용의 청각적 언어상상 과제를 수행토록 하였다. 이 두 가지 과제를 수행하면서 정량화뇌파검사를 시행하였고, 이때의 대뇌피질 활성의 차이를 paired t-test를 이용하여 분석하였다. 그리고 이러한 차이가 정신분열병 환자와 정상인에서 각기 어떤 식으로 달리 나타나는가 비교하였다. 결과 : 정상인의 경우 중립적 감정일 때에 비해 부정적 감정의 청각적 언어상상시, 좌측 측두엽 부위(TCP1)에서 beta주파수대의 뇌파 진폭이 증가하였고, 대뇌 우반구의 몇몇 부위(FP2, F4, C4, CP2, P4)에서 theta주파수대의 뇌파 진폭이 감소하였다. 그러나 정신분열병 환자의 경우, 두 가지 과제를 수행하는 동안 모든 주파수대에서 뇌파 진폭의 차이가 관찰되지 않았다. 결론 : 본 연구 결과는 좌측 측두엽의 더 많은 활성이 요구되는 부정적 내용의 청각적 언어상상을 하게 될 때, 정신분열병 환자에서는 적절한 활성화가 이루어지지 못하는 것을 지지하는 소견으로 생각된다. 그리고 이에 따른 자기감시체계의 활성의 저하가 환청과 밀접하게 관련될 수 있는 것으로 시사된다.

• 한국의학물리학회지:의학물리
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• 제16권1호
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• pp.32-38
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• 2005

작동기억 및 얼굴 영상에 대한 정보 처리 과정의 장애는 정신분열병 환자에서 나타나는 광범위한 인지기능 장애 중의 하나이다. 본 연구는 기능적 자기공명영상기법을 이용하여 정신분열병 환자군과 정상 대조군 간의 얼굴 영상의 작동기억에 관여하는 뇌 활성의 차이를 분석하고자 하였다 10명의 정신분열병 환자와 10명의 정상 대조군을 대상으로 선정하였다. 얼굴영상 자극을 이용한 1-back 작동기억 파라다임을 수행하는 동안 뇌 피질의 활성을 측정하기 위해 기능적 자기공명영상으로 두 군간의 뇌 활성의 차이를 SPM을 사용하여 분석하였다. 정신분열병 환자군은 정상대조군에 비해 작동기억 수행 점수가 유의하게 저하되어 있었다 환자군에서 대뇌의 좌측 방추상 이랑, 우측 위 전두 이랑, 양측 중간 전두 이랑, 도, 좌측 중간 측두 이랑, 설전부 피질과 소뇌의 사각엽과 충부의 활성이 감소되어 있었다. 반면, 외측 전전두 피질과 두정엽의 활성이 증가되었고, 또한 두 군 모두에서 우측반구의 활성이 증가되어 있었다. 정신분열병 환자에서 좌측 방추상 이랑의 활성이 감소된 것은 얼굴 영상에 대한 정보 처리 과정의 장애를 의미하며 기능적 자기공명영상분석법으로 작동기억능력의 유용성을 평가하였다.

• 수면정신생리
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• 제5권2호
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• pp.119-133
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• 1998

Attentional processes facilitate cognitive and behavioral performance in several ways. Attention serves to reduce the amount of information to receive. Attention enables humans to direct themselves to appropriate aspects of external environmental events and internal operations. Attention facilitates the selection of salient information and the allocation of cognitive processing appropriate to that information. Attention is not a unitary process that can be localized to a single neuroanatomical region. Before the cortical registration of sensory information, activation of important subcortical structures occurs, which is called as an orienting response. Once sensory information reaches the sensory cortex, a large number of perceptual processes occur, which provide various levels of perceptual resolution of the critical features of the stimuli. After this preattentional processing, information is integrated within higher cortical(heteromodal) systems in inferior parietal and temporal lobes. At this stage, the processing characteristics can be modified, and the biases of the system have a direct impact on attentional selection. Information flow has been traced through sensory analysis to a processing stage that enables the new information to be focused and modified in relation to preexisting biases. The limbic and paralimbic system play significant roles in modulating attentional response. It is labeled with affective salience and is integrated according to ongoing pressures from the motivational drive system of the hypothalamus. The salience of information greatly influences the allocation of attention. The frontal lobe operate response selection system with a reciprocal interaction with both the attention system of the parietal lobe and the limbic system. In this attentional process, the search with the spatial field is organized and a sequence of attentional responses is generated. Affective, motivational and appectitive impulses from limbic system and hypothalamus trigger response intention, preparation, planning, initiation and control of frontal lobe on this process. The reticular system, which produces ascending activation, catalyzes the overall system and increases attentional capacity. Also additional energetic pressures are created by the hypothalamus. As psychophysiological measurement, skin conductance, pupil diameter, muscle tension, heart rate, alpha wave of EEG can be used. Event related potentials also provide physiological evidence of attention during information process. NI component appears to be an electrophysiological index of selective attention. P3 response is developed during the attention related to stimulus discrimination, evaluation and response.