• Title/Summary/Keyword: Mouse Brain

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Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

  • Ju-Hyun Lee;Mohammed R. Shaker;Si-Hyung Park;Woong Sun
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.385-393
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    • 2023
  • In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell-cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

Inhibition of $NF-{\kappa}B$ Activation Increases Oxygen-Glucose Deprivation-Induced Cerebral Endothelial Cell Death

  • Lee, Jin-U;Kim, Chul-Hoon;Shim, Kyu-Dae;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.2
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    • pp.65-71
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    • 2003
  • Increasing evidences suggest that ischemia-induced vascular damage is an integral step in the cascade of the cellular and molecular events initiated by cerebral ischemia. In the present study, employing a mouse brain endothelioma-derived cell line, bEnd.3, and oxygen-glucose deprivation (OGD) as an in vitro stroke model, the role of nuclear factor kappa B (NF-${\kappa}B$) activation during ischemic injury was investigated. OGD was found to activate NF-${\kappa}B$ and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of $I{\kappa}B{\alpha}$. OGD did not change the amount of $I{\kappa}B{\alpha}$. The extents of OGD-induced cell death after 8 h, 10 h, 12 h and 14 h of OGD were 10%, 35%, 60% and 85%, respectively. Reperfusion following OGD did not cause additional cell death, indicating no reperfusion injury after ischemic insult in cerebral endothelial cells. Three known as NF-${\kappa}B$ inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-${\kappa}B$ activation and increased OGD-induced bEnd.3 cell death in a dose dependent manner. There were no changes in the protein levels of bcl-2, bax and p53 which are modulated by NF-${\kappa}B$ activity. These results suggest that NF-${\kappa}B$ activation might be a protective mechanism for OGD-induced cell death in bEnd.3.

A Study on the correlation between Sung-Jung' concept of Sasang Constitutional Medicine and Brain (사상의학(四象醫學)에 나타난 성정(性情)의 개념과 뇌(腦)와의 상관성에 관한 고찰)

  • Kim, Jong-Weon;Seul, Yu-Kyung
    • Journal of Sasang Constitutional Medicine
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    • v.12 no.2
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    • pp.17-33
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    • 2000
  • Purpose of this study is to investigate the correlation between Sung-Jung' concept of Sasang Constitutional Medicine and Brain. So, After studying the meaning of Sung-Jung' concept of Sasang Constitutional Medicine, I made a comparative study through the structure, function, development of Brain. The conclusions were as follows. 1. Human's brain acts a rational, control his actions. and It manage human body's physiology and pathology. and It perceive his surroundings, express his emotion through comprehension, synthesis, judgement about information from various fields. and It's abnormality bring about a spiritual, bodily injury. Therefore, human's brain have many correlation with Sung-Jung' concept of Sasang Constitutional Medicine. 2. Neocortex' function have many correlation with Sung' concept of Hearing-Sight-Smell-Taste (聽視嗅味=sensation=a highly mental capacity) through Ear-Eye-Nose-Mouse(耳目鼻?). 3. Limbic-system'function have many correlation with Jung' concept of Sorrow-Anger-Pleasure-Joy(哀怒喜榮=emotion) through Lung-Spleen-Liver-Kidney(肺脾肝腎) 4. Brain-stem' function have many correlation with vitalistic concept through Qui of Sorrow - Anger - Pleasure - Joy(哀怒喜樂之氣)' rise and fall. 5. Relation of emotions and diseases through Limbic system and Autonomic nervous system have many correlation with relation of Sung-Jung and diseases of Sasang Constitutional Medicine 6. Left-hemisphere' function that has superior power of verbal, analysis, logicality, consideration have many correlation with tendency of Soeumin and Taeumin. and Right-hemisphere' function that has superior power of emotion, non-verbal, imagination, spatial perception have many correlation with tendency of Soyangin and Taeyangin.

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Specific Interaction of Rat Vanilloid Receptor, TRPV1 with Rab11-FIP3 (Rat 바닐로이드 수용체 TRPV1과 Rab11-FIP3의 특이적 결합)

  • Lee, Soon-Youl;Kim, Mi-Ran
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.1
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    • pp.312-317
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    • 2011
  • Vanilloid receptor TRPV1 (known as capsaicin channel, transient receptor potential vanilloid 1) is known to be a key protein in the pain signal transduction. However, the proteins controlling the activity of the channel are not much known yet. Recently mouse Rab11-FIP3 (Rab11-family interaction protein 3) was found and reported to interact with rat TRPV1. Rab11 has been shown to play a key role in a variety of cellular processes including plasma membrane recycling, phagocytosis, and transport of secretory proteins from the trans-Golgi network. Therefore, Rab11-FIP3 was proposed to be involved in the membrane trafficking of TRPV1. In this study, the unreported rat Rab11-FIP3 was yet cloned in order to show the specific interaction of the TRPV1 and Rab11-FIP3 in the same species of rat and to examine the membrane trafficking of TRPV1. The result showed that rat Rab11-FIP3 is expected to have 489 amino acids and showed 80% identity with that of human and over 90% identity with that of mouse. Rab11-FIP3 was found to be expressed in heart, brain, kidney, testis using northern and western blot analyses. We also found that rat Rab11-FIP3 was colocalized with rat TRPV1 but not with TRPV2 of same family in the rat brain by using immunohistochemistry showing that two proteins interact specifically, suggesting the role of Rab11-FIP3 in the membrane trafficking.

A Study on New Gameplay Based on Brain-Computer Interface (BCI 기반의 새로운 게임 플레이 연구)

  • Ko, Min-Jin;Bae, Kyoung-Woo;Oh, Gyu-Hwan
    • 한국HCI학회:학술대회논문집
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    • 2009.02a
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    • pp.749-755
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    • 2009
  • BCI (Brain-Computer Interface) is a way to control computer by using the human brain waves. As the hardware using brain wave technologies has developed, former expensive and big sized brain wave measuring devices have recently become much smaller and cheaper in their prices, making it possible for the individuals to buy them. This predicts them to be applied in various fields of multimedia industry. This thesis is to give an insight into whether the BCI device can be used as a new gaming device approaching it in a game designing point of view. At first, we propose game play elements that can effectively utilizing the BCI devices and produce a game prototype adopting the BCI device based on such game play elements. Next, we verify it with statistical data analysis to show that the prototype adopting the BCI device gives more clear and efficient controls in its game play than a game of only adopting keyboard & mouse devices. The results will give a guideline for effective game design methodology for making BCI based games.

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A Study on New Gameplay Experience Based on Brain-Computer Interface (BCI를 기반으로 하는 플레이어의 새로운 게임플레이 경험 연구)

  • Ko, Min-Jin;Oh, Gyu-Hwan;Bae, Kyoung-Woo
    • Journal of Korea Game Society
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    • v.9 no.6
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    • pp.31-44
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    • 2009
  • BCI (Brain-Computer Interface) is a way to control computer by using the human brain waves. As the hardware using brain wave technologies has developed, former expensive and big sized brain wave measuring devices have recently become much smaller and cheaper in their prices, making it possible for the individuals to buy them. This predicts them to be applied in various fields of multimedia industry. This thesis is to give an insight into whether the BCI device can be used as a new gaming device approaching it in a game designing point of view. At first, we proposed game play elements that can effectively utilizing the BCI devices, systematize, and produced a game prototype adopting the BCI device based on such game play elements. Next, we verified it with statistical data analysis to show that the prototype adopting the BCI device gives more clear and efficient controls in its game play than a game of only adopting keyboard & mouse devices and analysis verified that BCI-based game play elements provide users with a more intuitive and interesting experience than traditional non-BcI-based game play elements. The results will give a guideline for effective game design methodology for making BCI based games.

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Spatio-Temporal Expression Pattern of Grp 78, a Putative Hoxc8 Downstream Target Gene, During Murine Embryogenesis

  • Kang Jin Joo;Kwon Yunjeong;Lee Eun Young;Park Hyoung Woo;Yang Hye-Won;Kim Myoung Hee
    • Biomedical Science Letters
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    • v.11 no.3
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    • pp.311-318
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    • 2005
  • Grp78, discovered as one of the putative target genes of Hoxc8, is a highly conserved stress protein and functions as a molecular chaperone in the endoplasmic reticulum (ER). In order to see the stage-specific expression pattern of Grp78 during development, mouse embryos from day 7.5 to 17.5 p.c. were isolated, and RT-PCR as well as in situ hybridization was performed. When RT-PCR was performed using Grp78 specific primers, periodic expression pattern was detected. And also a region-specific expression pattern was detected with a strong expression in the trunk part of day 11.5 p.c. embryo, like that of Hoxc8. When in situ hybridization was performed, Grp78 was revealed to be expressed in the endoderm, somite, neuroepithelium cells of neural tube in early embryos. In the case of late embryos, Grp78 expression was detected in the liver, segmental bronchus within cranial lobe of lung, ossification center within the cartilage primordium of rib and vertebra, submandibular gland, as well as metanephros. These expression patterns are very much similar to those of Hoxc8. Since Hoxc8 has been reported to regulate apoptosis during organogenesis, it might be possible that the apoptotic function could have been conveyed through the expression of Grp78, implying that the Grp78 is one of the Hoxc8 downstream target genes.

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Genome-Wide Analysis Identifies NURR1-Controlled Network of New Synapse Formation and Cell Cycle Arrest in Human Neural Stem Cells

  • Kim, Soo Min;Cho, Soo Young;Kim, Min Woong;Roh, Seung Ryul;Shin, Hee Sun;Suh, Young Ho;Geum, Dongho;Lee, Myung Ae
    • Molecules and Cells
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    • v.43 no.6
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    • pp.551-571
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    • 2020
  • Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.

The Epithelial-Mesenchymal Transition During Tooth Root Development

  • Kang, Jee-Hae;Park, Jin-Ho;Moon, Yeon-Hee;Moon, Jung-Sun;Kim, Sun-Hun;Kim, Min-Seok
    • International Journal of Oral Biology
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    • v.36 no.3
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    • pp.135-141
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    • 2011
  • Hertwig's epithelial root sheath (HERS) consists of bi-layered cells derived from the inner and outer dental epithelia and plays important roles in tooth root formation as well as in the maintenance and regeneration of periodontal tissues. With regards to the fate of HERS, and although previous reports have suggested that this entails the formation of epithelial rests of Malassez, apoptosis or an epithelial-mesenchymal transformation (EMT), it is unclear what changes occur in the epithelial cells in this structure. This study examined whether HERS cells undergo EMT using a keratin-14 (K14) cre:ROSA 26 transgenic reporter mouse. The K14 transgene is expressed by many epithelial tissues, including the oral epithelium and the enamel organ. A distinct K14 expression pattern was found in the continuous HERS bi-layer and the epithelial diaphragm were visualized by detecting the ${\beta}$-galactosidase (lacZ) activity in 1 week postnatal mice. The 2 and 4 week old mice showed a fragmented HERS with cell aggregation along the root surface. However, some of the lacZ-positive dissociated cells along the root surface were not positive for pan-cytokeratin. These results suggest that the K14 transgene is a valuable marker of HERS. In addition, the current data suggest that some of the HERS cells may lose their epithelial properties after fragmentation and subsequently undergo EMT.

Development of Computerized Neuropsychological Tests for Functional Localization of Brain (뇌의 기능적 국소화를 위한 전산화 신경심리 검사의 개발)

  • Lee, Sung-Hoon;Ahn, Chang-Bum;Park, Hae-Jung
    • Sleep Medicine and Psychophysiology
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    • v.6 no.2
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    • pp.149-157
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    • 1999
  • A Computerzed Neuropsychological Test(CNT) system using multimedia and object oriented technologies are developed for clinical application in psychiatry. The developed system is composed of 14 neuropsychologial tests which are capable of evaluation of various cognitive functions and functional localization of brain. The system employs Microsoft Window based graphic user interface for easy operation and it has a touch screen and a mouse as input devices from the patient. Speech perception test, color word test, verbal memory test, contingent continuos performance test, and trail making test were translated into korean language, so that usefulness of tests was maximized. Through the results of utilization of this system in the cases of patients with head trauma and psychiatric desorder, this system can be proved to be useful in the evaluation of cognitive function and functional localization of brain.

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