• Journal of Ginseng Research
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• v.46 no.3
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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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• v.20 no.6
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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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• v.42 no.1
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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.

• Korean Journal of Cognitive Science
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• v.24 no.1
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• pp.1-24
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• 2013

The elderly population continues to increase in Korea and there has been a growing interest in understanding normal aging. In response to this public interest, the present paper reviewed human aging research focusing on recently published neuroimaging studies. For the first half of the paper, I reviewed the effects of aging on the brain and cognition. In normal aging, structural changes in the brain include atrophy and volume reduction in the prefrontal and temporal cortices. Functional changes are exhibited in the form of overactivation of the brain. Moreover, age-related cognitive decline is particularly observed in inhibition and memory, which are also associated with the age-related structural changes in the brain. For the second half of the paper, I introduced physical exercise studies showing that exercise played a protective role in the age-related neurocognitive decline. More specifically, engaging in physical exercise (particularly, aerobic exercise) for a relatively long period of time (e. g., > 6 mon.) protected older adults from volume loss in the prefrontal cortex and the hippocampus, and induced better inhibition and memory. These exercise-induced benefits appear to be associated with changes in neuronal levels, indicating that the aging brain is still plastic and this plasticity can be enhanced by physical exercise.

• BMB Reports
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• v.46 no.2
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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.

• Therapeutic Science for Rehabilitation
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• v.1 no.2
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• pp.35-40
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• 2012

The purpose of this review was to investigate feasibility of intensive virtual reality training to improve upper extremity function with brain plasticity of individuals with stroke through the literature. The recovery of the paretic upper extremity depends on regularity and intensity of training as use-dependent plasticity. In resent, virtual reality program has been widely used in the occupational therapy field of augmented stroke rehabilitation. There is a growing body of evidence that virtual reality training of the paretic extremity induces brain plasticity associated with motor improvement. In terms of therapeutic feasibility to improve paretic upper extremity, recent research has explored several important factors of virtual reality training for recovery of upper extremity motor function. These factors include high repetition intensity, high motivation like type of game, enhanced multisensory feedback regarding performance, and interactive task-oriented training. Therefore, occupational therapy combined with intensive and repetitive virtual reality training will enhance recovery of upper extremity motor function after stroke.

• Journal of Korean Neurosurgical Society
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• v.39 no.2
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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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• v.37 no.11
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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.

• Journal of Korean Elementary Science Education
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• v.26 no.1
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.6
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• pp.467-477
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• 2001

We examined astrocyte regional heterogeneity in their morphological changes in response to various stimuli. Astrocytes were cultured from six different neonatal rat brain regions including cerebral cortex, hippocampus, cerebellum, mid brain, brain stem and hypothalamus. Astrocyte stellation was induced by serum deprivation and the maximum stellation in different regional astrocytes was achieved after 2 h. After 24 h, in all astrocyte cultures, the level of stellation returned to their original level. Cerebellar or hypothalamic astrocytes were the most or the least sensitive, respectively, to serum deprivation. The order of maximum sensitivity to serum deprivation among different regional astrocytes was: cerebellum＞mid $brain{\ge}hippocampus,\;brain\;stem{\ge}cerebral$ cortex＞hypothalamus. Isoproterenol-induced astrocyte stellation was also examined in different regional astrocytes, and similar order of maximum sensitivity as in serum deprivation was observed. Next a possible developmental effect on astrocyte morphological changes was examined in cerebral cortex and cerebellum astrocytes cultured from postnatal day 1 (P1), P4 and P7 rat brains. A much higher sensitivity of cerebellum astrocytes to serum deprivation as well as isoproterenol treatment was consistently observed in P1, P4 and P7-derived astrocytes compared to cerebral cortex astrocytes. The present study demonstrates different regional astrocytes maintain different levels of morphological plasticity in vitro.