• 생물정신의학
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• 제8권1호
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• pp.3-19
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• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

• Journal of Ginseng Research
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• 제46권3호
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• pp.376-386
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• 2022

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.557-564
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• 2016

Metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), a type of synaptic plasticity, is characterized by a reduction in the synaptic response, mainly at the excitatory synapses of the neurons. The hippocampus and the cerebellum have been the most extensively studied regions in mGluR-dependent LTD, and Group 1 mGluR has been reported to be mainly involved in this synaptic LTD at excitatory synapses. However, mGluR-dependent LTD in other brain regions may be involved in the specific behaviors or diseases. In this paper, we focus on five cortical regions and review the literature that implicates their contribution to the pathogenesis of several behaviors and specific conditions associated with mGluR-dependent LTD.

• Molecules and Cells
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• 제42권1호
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• pp.28-35
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• 2019

Animals need to be able to alter their developmental and behavioral programs in response to changing environmental conditions. This developmental and behavioral plasticity is mainly mediated by changes in gene expression. The knowledge of the mechanisms by which environmental signals are transduced and integrated to modulate changes in sensory gene expression is limited. Exposure to ascaroside pheromone has been reported to alter the expression of a subset of putative G protein-coupled chemosensory receptor genes in the ASI chemosensory neurons of C. elegans (Kim et al., 2009; Nolan et al., 2002; Peckol et al., 1999). Here we show that ascaroside pheromone reversibly represses expression of the str-3 chemoreceptor gene in the ASI neurons. Repression of str-3 expression can be initiated only at the L1 stage, but expression is restored upon removal of ascarosides at any developmental stage. Pheromone receptors including SRBC-64/66 and SRG-36/37 are required for str-3 repression. Moreover, pheromone-mediated str-3 repression is mediated by FLP-18 neuropeptide signaling via the NPR-1 neuropeptide receptor. These results suggest that environmental signals regulate chemosensory gene expression together with internal neuropeptide signals which, in turn, modulate behavior.

• 인지과학
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• 제24권1호
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• pp.1-24
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• 2013

한국 사회에서 고령 인구가 지속적으로 증가하고 있는 추세에 발맞추어 본 논문은 노화과정에서 일어나는 뇌의 구조, 기능적 변화 및 인지 기능의 저하를 살펴보고, 고령화 대처의 한 방안으로 제안되고 있는 운동의 효과에 관하여 인지신경과학적 연구를 중심으로 개관하였다. 정상 노화 과정에서 일어나는 뇌의 변화는 전전두엽과 측두엽(해마 포함)의 부피변화와 함께 인지 과제 수행 시 과잉활성화와 같은 현상들이다. 이러한 뇌의 변화와 함께 인지 기능의 저하도 관찰되는데 주로 억제 및 기억 기능의 저하가 노화를 특징짓는 인지기능의 변화로 알려져 왔다. 이와 같은 노화 관련 뇌인지의 퇴행적 변화에 대응할 수 있는 보호적 요인 중 하나가 운동이다. 실제 노인을 대상으로 장기간 운동 프로그램을 실시한 연구 결과들은 참가 노인들의 전두엽과 측두엽, 특히 해마의 위축이 개선되고 억제와 기억 기능 역시 향상되었음을 보고하였다. 이러한 결과는 뇌세포 단위에서의 변화로부터 시작하여 노화하는 뇌 역시 변화할 수 있고, 운동이 이러한 긍정적인 변화를 유도할 수 있음을 보여준다.

• BMB Reports
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• 제46권2호
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• pp.103-106
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• 2013

Phosphoinositide 3-kinases (PI3Ks) play key roles in synaptic plasticity and cognitive functions in the brain. We recently found that genetic deletion of $PI3K{\gamma}$, the only known member of class IB PI3Ks, results in impaired N-methyl-D-aspartate receptor-dependent long-term depression (NMDAR-LTD) in the hippocampus. The activity of RalA, a small GTP-binding protein, increases following NMDAR-LTD inducing stimuli, and this increase in RalA activity is essential for inducing NMDAR-LTD. We found that RalA activity increased significantly in $PI3K{\gamma}$ knockout mice. Furthermore, NMDAR-LTD-inducing stimuli did not increase RalA activity in $PI3K{\gamma}$ knockout mice. These results suggest that constitutively increased RalA activity occludes further increases in RalA activity during induction of LTD, causing impaired NMDAR-LTD. We propose that $PI3K{\gamma}$ regulates the activity of RalA, which is one of the molecular mechanisms inducing NMDAR-dependent LTD.

• 재활치료과학
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• 제1권2호
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• pp.35-40
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• 2012

본 연구에서는 가상현실 치료가 뇌졸중 환자의 뇌 가소성을 동반한 상지기능 향상에 미치는 영향을 알아보고 강도 높은 가상현실 훈련이 뇌졸중 환자의 상지기능 향상을 위한 집중치료로써 임상적으로 유용한 훈련인지 알아보고자 하였다. 뇌졸중 환자에게 있어 사용-의존성 즉 운동 강도와 반복은 마비 측 사지의 운동 기능향상에 중요한 치료적 요소이다. 최근에는 상지의 지속적 사용을 통한 뇌-가소성에 기반한 변화를 유도할 수 있는 치료방법으로 가상현실 치료가 대두되었다. 가상현실 치료는 재활 임상환경에서 운동기능 향상을 위한 훈련강도와 반복을 제공할 수 있는 기술적 방법으로 채택되기 시작하였다. 특히 뇌졸중 환자의 상지 기능을 향상시키기 위한 치료적 유용성 측면에서는 강도 높은 반복적 훈련이 가능하다는 것과 게임 같은 형식으로 높은 동기부여가 가능하다는 것, 실제 수행을 통한 다중감각적 피드백 제공, 상호작용이 가능한 과제지향적 치료가 가능하다는 장점을 가지고 있다. 임상 환경에서 작업치료와 더불어 부가적으로 가상현실 치료를 실시하는 것은 뇌졸중 환자의 상지 기능회복을 더욱 촉진할 것이다.

• Journal of Korean Neurosurgical Society
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• 제39권2호
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• pp.130-135
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• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• Molecules and Cells
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• 제37권11호
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• 한국초등과학교육학회지:초등과학교육
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• 제26권1호
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• pp.49-62
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• 2007

The higher cognitive functions of the human brain including teaming are hypothesized to be selectively distributed across large-scale neural networks interconnected to the cortical and subcortical areas. Recently, advances in functional imaging have made it possible to visualize the brain areas activated by certain cognitive activities in vivo. Neural substrates for teaming and motivation have also begun to be revealed. Functional magnetic resonance imaging (fMRI) provides a non-invasive indirect mapping of cerebral activity, based on the blood- oxygen level dependent (BOLD) contrast which is based on the localized hemodynamic changes following neural activities in certain areas of the brain. The fMRI method is now becoming an essential tool used to define the neuro-functional mechanisms of higher brain functions such as memory, language, attention, learning, plasticity and emotion. Further research in the field of education will accelerate the verification of the effects on loaming or help in the selection of model teaching strategies. Thus, the purpose of this study was to review brain study methods using fMRI in science education. In conclusion, a number of possible strategies using fMRI for the study of elementary science education were suggested.