• Investigative Magnetic Resonance Imaging
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• 제3권1호
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• pp.41-46
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• 1999

목적 : 뇌기능 영상을 이용하여 자극에 따른 시각영역, 운동영역 및 소뇌에서의 총활성화의 차이를 연구하고자 하였다. 대상 및 방법 : 건강한 5명의 피실험자를 대상으로 EP 기법을 이용하여 시각자극과 운동자극에 의한 피질활성화 검사를 시행하였다. 시각피질 활성화를 위해서는 LED 자극과 Checker-Board 자극을 각각 행하였고, 운동피질과 소뇌의 활성화를 위해서는 엄지손가락 운동과 네 손가락을 엄지 손가락과 순서대로 마주치게 하는 운동을 시행하였다. 각각의 자극은 60초의 휴식기, 120초의 자극기 및 운동기, 다시 60초의 휴식기로서 시행하였다. 데이터 처리는 cros-correlation 방법으로 통게처리 하였고, 적절한 문턱 값 이상을 가지는 화소를 활성화 화소로 정의하였다. 이 활성화 화소의 수와 신호변화율의 곱으로서 총활성화의 시간축 데이타를 완성하였다. 결과 : 시각피질에서의 총활성화는 Checker-Board 자극에 비해 LED 자극을 가했을 때 100% 이상 증가하였다. 엄지 손가락 운동에 비해 손가락 마주치기 운동을 시행했을 때 총활서와는 운동피질에서 100% 이상 증가하였고, 소뇌에서는 150% 이상 증가하였다. 결론 : 시각 및 운동자극의 변화에 따라 시각영역, 운동영역 및 소뇌에서의 총활성화가 차이를 보이는 것을 확인할 수 있었다.

• Nutrition Research and Practice
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• 제11권5호
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• pp.381-387
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• 2017

BACKGROUND/OBJECTIVES: Vascular dementia (VaD) caused by reduced blood supply to the brain manifests as white matter lesions accompanying demyelination and glial activation. We previously showed that arabinoxylan consisting of arabinose and xylose, and arabinose itself attenuated white matter injury in a rat model of VaD. Here, we investigated whether larch arabinogalactan (LAG) consisting of arabinose and galactose could also reduce white matter injury. MATERIALS/METHODS: We used a rat model of bilateral common carotid artery occlusion (BCCAO), in which the bilateral common carotid arteries were exposed and ligated permanently with silk sutures. The rats were fed a modified AIN-93G diet supplemented with LAG (100 mg/kg/day) for 5 days before and 4 weeks after being subjected to BCCAO. Four weeks after BCCAO, the pupillary light reflex (PLR) was measured to assess functional consequences of injury in the corpus callosum (cc). Additionally, Luxol fast blue staining and immunohistochemical staining were conducted to assess white matter injury, and astrocytic and microglial activation, respectively. RESULTS: We showed that white matter injury in the the cc and optic tract (opt) was attenuated in rats fed diet supplemented with LAG. Functional consequences of injury reduction in the opt manifested as improved PLR. Overall, these findings indicate that LAG intake protects against white matter injury through inhibition of glial activation. CONCLUSIONS: The results of this study support our hypothesis that cell wall polysaccharides consisting of arabinose are effective at protecting white matter injury, regardless of their origin. Moreover, LAG has the potential for development as a functional food to prevent vascular dementia.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.515-521
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• 1997

Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

• Molecules and Cells
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• 제21권2호
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• pp.237-243
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• 2006

Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.279-286
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• 1998

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

• The Korean Journal of Physiology and Pharmacology
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• 제10권5호
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• pp.243-249
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• 2006

The effect of genistein, widely used as a specific tyrosine kinase inhibitor, on rat brain Kv1.5 channels which were stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Genistein inhibited Kv1.5 currents at +50 mV in a concentration-dependent manner, with an $IC_{50}$ of $54.7{\pm}8.2\;{\mu}M$ and a Hill coefficient of $1.1{\pm}0.2$. Pretreatment of Kv1.5 with protein tyrosine kinase inhibitors ($10\;{\mu}M$ lavendustin A and $100\;{\mu}M$ AG1296) and a tyrosine phosphatase inhibitor ($500\;{\mu}M$ sodium orthovanadate) did not block the inhibitory effect of genistein. The inhibition of Kv1.5 by genistein showed voltage-independence over the full activation voltage range positive to 0 mV. The activation (at +50 mV) kinetics was significantly delayed by genistein: time constant for an activation of $1.4{\pm}0.2$ msec under control conditions and $10.0{\pm}1.5$ msec in the presence of $60\;{\mu}M$ genistein. Genistein also slowed the deactivation of the tail currents, resulting in a crossover phenomenon: a time constant of $11.4{\pm}1.3$ msec and $40.0{\pm}4.2$ msec under control conditions and in the presence of $60\;{\mu}M$ genistein, respectively. Inhibition was reversed by the application of repetitive depolarizing pulses, especially during the early part of the activating pulse. These results suggest that genistein directly inhibits Kv1.5 channels, independent of phosphotyrosine-signaling pathway.

• 운동영양학회지
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• 제16권2호
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• pp.73-84
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• 2012

Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.

• 대한방사선기술학회지:방사선기술과학
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• 제34권1호
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• pp.17-25
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• 2011

본 연구는 만성적인 망간(Mn) 노출 결과로써 초래될 수 있는 영향을 기능적 신경영상기법의 하나인 fMRI(functional magnetic resonance imaging)를 이용하여 인지 활동에 따른 뇌 활성화 정도를 분석, 평가하고자 하였다. 조선소에서 10년 이상 용접 작업을 해왔고 현재도 용접 전담 업무를 하고 있는 34세 이상의 남성 15명을 노출군으로 하였고, 노출군과 연령, 사회·경제적 지위와 행동 패턴이 비슷하며 다른 위험한 금속성 물질에 노출되지 않은 제조업 사업장에서 용접 작업을 하지 않는 생산직 근로자 15명을 대조군으로 구성하여 설문조사와 혈액 검사, fMRI를 실시하였다. 그 결과 fMRI 대상자(29명)의 평균 혈중 Mn 농도는 노출군($1.3\;{\mu}g/dl$)이 대조군($0.8\;{\mu}g/dl$)보다 유의하게 증가하였고, Pallidal Index(PI)도 노출군이 대조군보다 유의하게 증가하였다(p < 0.001). MRI 상의 PI값은 혈중 Mn 농도가 $0.93\;{\mu}g/dl$ 이상인 군이 $0.93\;{\mu}g/dl$ 미만인 군보다 유의하게 증가하였다(p < 0.001). 산술 과제를 수행하는 동안 실험군의 각 문항에 대한 평균 응답 시간은 노출군(1.3 sec)이 대조군(1.1 sec)보다 유의하게 증가하였다. 또한, 문항 전체에 대한 평균 응답 시간도 대조군(54.7 sec)이 노출군(45.0 sec)보다 느리게 나타났으며, 통계학적으로도 유의미한 차이를 보였다(p < 0.001). 대조군의 뇌 활성화 영역은 후두피질의 좌 우측, 상 중간전두피질과 하두정피질(inferior parietal cortex)의 우측, 중간측두피질의 좌측 영역에서 유의하게 증가하였다. 노출군의 뇌 활성화 영역은 대조군의 활성화 영역과 비슷한 위치에서는 보다 넓고 높은 활성화 상태를 보였다. 노출군은 대조군의 활성화 영역에 추가하여 상 하 측두피질의 우측, 뇌섬엽의 좌측, 뇌교량과 측뇌실 영역에서 유의한 증가로 나타났다. 두 집단간 뇌 활성화 영역 비교를 위한 t-test에서 노출군은 중간측두피질 영역을 포함하여 우측 하측두피질, 좌측 상두정피질, 좌측 후두피질, 좌측 소뇌 등의 영역에서 대조군보다 유의하게 더 높은 증가를 나타냈다. 하지만 어떤 영역도 노출군보다 대조군에서 더 활성화된 영역은 없었다. 이상의 결과에서 만성적인 Mn 노출은 인지 과제 수행 중에 뇌 활성화를 증가시켰다. 동일한 과제에서도 상 하 측두피질, 뇌도 영역에서 활성화가 증가되었고, 노출군이 일반인보다 측두영역 및 후두영역에서 뇌 활성화 상태가 증가되었음을 알아냈다. 이상의 결과에서 살펴 볼 때 작업환경 내에서의 만성적인 Mn 노출이 뇌 활성화의 신경 네트워크에 영향을 미친다는 것이 확인되었다.

• 한국환경보건학회지
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• 제37권2호
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• pp.102-112
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• 2011

Objectives: The purpose of this study is to analyze the effects of chronic exposure by welders to manganese (Mn) through an analysis of the degree of brain activity in different activities such as cognition and motor activities using the neuroimaging technique of functional magnetic resonance imaging (fMRI). The neurotoxic effect that Mn has on the brain was examined as well as changes in the neuro-network in motor areas, and the usefulness of fMRI was evaluated as a tool to determine changes in brain function from occupational exposure to Mn. Methods: A survey was carried out from July 2010 to October 2010 targeting by means of a questionnaire 160 workers from the shipbuilding and other manufacturing industries. Among them, 14 welders with more than ten years of job-related exposure to Mn were recruited on a voluntary basis as an exposure group, and 13 workers from other manufacturing industries with corresponding gender and age were recruited as a control group. A questionnaire survey, a blood test, and an fMRI test were carried out with the study group as target. Results: Of 27 fMRI targets, blood Mn concentration of the exposure group was significantly higher than that of the control group (p<0.001), and Pallidal Index (PI) of the welder group was also significantly higher than that of the control group (p<0.001). As a result of the survey, the score of the exposure group in self-awareness of abnormal nerve symptoms and abnormal musculoskeletal symptoms was higher than those of the control group, and there was a significant difference between the two groups (p<0.05, respectively). In the correlation between PI and the results of blood tests, the correlation coefficient with blood Mn concentration was 0.893, revealing a significant amount of correlation (p<0.001). As for brain activity area within the control group, the right and the left areas of the superior frontal cortex showed significant activity, and the right area of superior parietal cortex, the left area of occipital cortex and cerebellum showed significant activity. Unlike the control group, the exposure group showed significant activity selectively on the right area of premotor cortex, at the center of supplementary motor area, and on the left side of superior temporal cortex. In the comparison of brain activity areas between the two groups, the exposure group showed a significantly higher activation state than did the control group in such areas as the right and the left superior parietal cortex, superior temporal cortex, and cerebellum including superior frontal cortex and the right area of premotor cortex. However, in nowhere did the control group show a more activated area than did the exposure group. Conclusions: Chronic exposure to Mn increased brain activity during implementation of hand motor tasks. In an identical task, activation increased in the premotor cortex, superior temporal cortex, and supplementary motor area. It was also discovered that brain activity increase in the frontal area and occipital area was more pronounced in the exposure group than in the control group. This result suggests that chronic exposure to Mn in the work environment affects brain activation neuro-networks.

• 대한의용생체공학회:의공학회지
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• 제28권1호
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• pp.55-65
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• 2007

This paper sought to investigate pupil size variability, pupil size parameters in terms of time domain and frequency domain, the autonomic activity change induced by posture change, degree of sleepiness and cognitive task (math task). With a specially designed pupil image acquisition system in the dark room, these three kinds of experiments were performed to induce a dominant state of sympathetic or parasympathetic activation. Electrocardiogram and pupil size were measured in all the experiments. Based on three experiments, we calculated heart rate variability. In the pupil size analysis, we calculated the mean and standard deviation of pupil size (in time domain), and proposed several frequency bands that exhibit different autonomic activation between different sessions. The results indicate that in terms of heart rate variability, posture change exhibited significant differences but not between sleepiness level, or between cognitive task. Pupil sizes differed only during the postures. And we found some frequency bands that correlated with autonomic activation in each experiment. While heart rate variability reflects posture change that need cardiac control, pupil size variability reflects not only posture induced autonomic activation but sleepiness and cognitive load, which is processed in the brain, in time and frequency domain parameter.