• PNF and Movement
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• 제6권2호
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• pp.31-38
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• 2008

Purpose: The purpose of this study were to overview the effect of exercise on neural plasticity and the proteins related to neural plasticity. Results: Exercise increased levels of BDNF(brain-derived neurotrophic factor), Insulin-like growth factor-I (IGF-I), Synapsin, Synaptophysin, VEGF(vascular endothelial growth factor) and other growth factors, stimulate neurogenesis, increase resistance to brain insult and improve learning and mental performance. These proteins improved synaptic plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by strengthening the underlying systems that support plasticity including neurogenesis, metabolism and vascular function. Conclusion: Exercise-induced structural and functional change by these proteins can effect on functional movement, cognition in healthy and brain injured people and animals.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.1-8
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• 2016

Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

• 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.

• BMB Reports
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• 제50권5호
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• pp.237-246
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• 2017

Synapse is the basic structural and functional component for neural communication in the brain. The presynaptic terminal is the structural and functionally essential area that initiates communication and maintains the continuous functional neural information flow. It contains synaptic vesicles (SV) filled with neurotransmitters, an active zone for release, and numerous proteins for SV fusion and retrieval. The structural and functional synaptic plasticity is a representative characteristic; however, it is highly vulnerable to various pathological conditions. In fact, synaptic alteration is thought to be central to neural disease processes. In particular, the alteration of the structural and functional phenotype of the presynaptic terminal is a highly significant evidence for neural diseases. In this review, we specifically describe structural and functional alteration of nerve terminals in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD).

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.230-239
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• 2020

Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear. Here, the effects of imipramine on dendritic spine density and morphology in BLA and mPFC subregions of stressed mice were examined. Chronic restraint stress caused depressive-like behaviors such as enhanced social avoidance and despair level coincident with differential changes in dendritic spine structure. Chronic stress enhanced dendritic spine density in the lateral nucleus of BLA with no significant change in the basal nucleus of BLA, and altered the proportion of stubby or mushroom spines in both subregions. Conversely, in the apical and basal mPFC, chronic stress caused a significant reduction in spine density. The proportion of stubby or mushroom spines in these subregions overall reduced while the proportion of thin spines increased after repeated stress. Interestingly, most of these structural alterations by chronic stress were reversed by imipramine. In addition, structural changes caused by stress and blocking the changes by imipramine were corelated well with altered activation and expression of synaptic plasticity-promoting molecules such as phospho-CREB, phospho-CAMKII, and PSD-95. Collectively, our data suggest that imipramine modulates stress-induced changes in synaptic structure and synaptic plasticity-promoting molecules in a coordinated manner although structural and molecular alterations induced by stress are distinct in the BLA and mPFC.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.75-82
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• 2006

Synaptic plasticity, which is a long lasting change in synaptic efficacy, underlies many neural processes like learning and memory. It has long been acknowledged that new protein synthesis is essential for both the expression of synaptic plasticity and memory formation and storage. Most of the research interests in this field have focused on the events regulating transcriptional activation of gene expression from the cell body and nucleus. Considering extremely differentiated structural feature of a neuron in CNS, a neuron should meet a formidable task to overcome spatial and temporal restraints to deliver newly synthesized proteins to specific activated synapses among thousands of others, which are sometimes several millimeters away from the cell body. Recent advances in synaptic neurobiology has found that almost all the machinery required for the new protein translation are localized inside or at least in the vicinity of postsynaptic compartments. These findings led to the hypothesis that dormant mRNAs are translationally activated locally at the activated synapse, which may enable rapid and delicate control of new protein synthesis at activated synapses. In this review, we will describe the mechanism of local translational control at activated synapses focusing on the role of cytoplasmic polyadenylation of dormant mRNAs.

• BMB Reports
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• 제51권8호
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• pp.369-370
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• 2018

In previous studies, memory storage was localized to engram cells distributed across the brain. While these studies have provided an individual cellular profile of engram cells, their synaptic connectivity, or whether they follow Hebbian mechanisms, remains uncertain. Therefore, our recent study investigated whether synapses between engram cells exhibit selectively enhanced structural and functional properties following memory formation. This was accomplished using a newly developed technique called "dual-eGRASP". We found that the number and size of spines on CA1 engram cells that receive inputs from CA3 engram cells were larger than at other synapses. We further observed that this enhanced connectivity correlated with induced memory strength. CA3 engram synapses exhibited increased release probability, while CA1 engram synapses produced enhanced postsynaptic responses. CA3 engram to CA1 engram projections showed strong occlusion of long-term potentiation. We demonstrated that the synaptic connectivity of CA3 to CA1 engram cells was strengthened following memory formation. Our results suggest that Hebbian plasticity occurs during memory formation among engram cells at the synapse level.

• Applied Microscopy
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• 제36권2호
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• pp.83-91
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• 2006

신경연접은 다양한 생리적 또는 병적 상태에 반응하여 구조 및 수적 변화를 보이며, 신경연접의 밀도 변화는 신경세포의 활성 조절에 중요한 역할을 하는 것으로 알려져 있다. 따라서 특정 생리적 또는 병적 상태에서 신경연접의 밀도 변화를 명확히 이해하기 위해서는 정확한 정량방법을 이용한 밀도 측정이 필수적이다. 본 연구에서는 physical disector법을 이용하여 흰쥐 뇌의 치아이랑에 위치하는 과립신경세포의 신경연접 수를 측정하였으며, 이를 통해 physical disector의 방법적 정확성을 확인하고자 하였다. 성체 흰쥐를 관류고정한 후 치아이랑의 연속 절편을 얻어 통상적인 전자현미경 시료제작법을 통해 Epon 혼합용액에 포매하였다. Physical disector법을 이용한 밀도 분석 시 연속절편의 정렬, 비교 및 disector frame이 필요하므로 Reconstruct 프로그램을 사용하였다. 동물 당 40장의 $1{\mu}m$ 연속절편을 제작하여 과립신경세포체의 밀도를 측정하였으며, 15장의 80nm연속절편으로부터 bidirectional disector법을 이용하여 과립신경세포와 내측 관통로(medial perforant path) 간 신경 연접의 밀도를 분석하였다. 과립신경세포의 세포체와 신경연접은 각각 과립층과 분자층에 위치하기 때문에 하나의 신경세포가 가지는 신경연접의 수를 측정하기 위해서는 각 층의 부피를 고려하는 것이 요구된다. 따라서 과립층에 대한 분자층의 부피비율을 측정하였다. 실험결과, 흰쥐 치아이랑에 위치하는 하나의 과립세포당 약 6,500개의 신경연접의 존재한다는 사실을 확인하였으며, 이는 다른 연구자들의 결과와 유사하였다. 본 연구로부터 physical disector법은 특정 생리적 또는 병적 조건에서 나타나는 신경세포 및 신경연접의 수적 변화를 정확히 측정할 수 있는 유용한 정량방법임을 알 수 있었다. 향후 physical disector법을 이용하여 다양한 실험동물모델의 신경연접 변화를 분석하는 것은 신경연접의 형태적 가소성을 이해하는데 이바지할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.39-48
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• 2023

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED₅₀ of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

• 감성과학
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• 제24권2호
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• pp.39-48
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• 2021

국제통증연구학회(IASP)에 따르면, 신경병증성 통증은 정상 조건에서 중추신경계에 유해한 정보를 전달하는 신경계 기능 장애로 특징 지워진다. 이런 통증은 말초 혹은 중추 신경계에 확인 가능한 병변이 있는 질환과 어떠한 신경에도 병변이 없는 상태에서 발생하는 상황으로 나누어 볼 수 있다. 두 가지 상황 모두 장기적이고 만성적인 변화과정을 겪게 되며, 결과적으로 신경계가 부적절하게 적응하여 치유되기 어려운 만성통증 증후군으로 발전할 수 있다. 그러나 이러한 통증 치료는 진단에서부터 치료까지의 과정이 어려운 탓에 현재까지도 특별한 해결방안이 부족한 실정이다. 최근 자기공명영상(fMRI), 양전자방출단층촬영법(PET), 광영상(optical imaging) 등 영상분석기술이 발달함에 따라 통증을 유발할 수 있는 유해 자극에 대한 중추신경계의 반응을 영상화하는 연구가 증가하고 있다. 이러한 영상 기법들을 통해 통증을 해석하고 처리하는 뇌 영역에서 시냅스 간 가소성 변화가 일어나고 있음을 확인하였으며, 신경병증성 통증을 비롯한 만성통증과 학습과의 상호 작용을 이해하는 데 많은 도움을 주고 있다. 본 연구는 병리적 통증의 기전과 통증 자극에 따른 뇌의 구조적, 기능적 변화에 대해 최근까지 밝혀진 연구들을 소개하고자 한다. 만성적 통증의 정의와 발생기전을 되짚고 새로운 연구 동향을 살펴보는 것은 통증을 완화할 수 있는 방안을 강구하는 데 도움이 될 것으로 사료된다.