• PNF and Movement
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• v.6 no.2
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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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• v.20 no.1
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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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• 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.

• BMB Reports
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• v.50 no.5
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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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• v.28 no.3
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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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• v.14 no.2
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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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• v.51 no.8
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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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• v.36 no.2
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• pp.83-91
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• 2006

The number and structure of synapses are dynamically changed in response to diverse physiological and pathological conditions. Since strength of synaptic transmission is closely related to the synaptic density on a neuron, both synaptogenesis and synapse loss may play important roles in controlling neuronal activity. Thus it is essential to estimate the number of synapses using an accurate quantitative method for better understanding of the numerical alteration of synapses under terrain experimental conditions. We applied physical disector principle to estimating the number of synapses per neuron in the dentate gyrus of adult mice. First, we measured the numerical density of granule cells using the physical disector principle. Second, the density of medial perforant path to granule cell synapses was estimated using the bidirectional physical disector. Then, the volume ratio of molecular layer to granule cell layer was measured. With these numerial values, we successfully calculated the number of synapses per neuron. Individual granule cells have approximately 6500 synapses in the dentate gyrus of adult mice $(6,545{\pm}330)$, which are comparable to those of other researchers. Our results showed that the estimation of synapse numbers per neuron using the physical disector principle would provide accurate and precise information on the numerical alteration of synapses in diverse physiological and pathological conditions. Following analyses of synapse numbers using this method will contribute to the better understanding of structural synaptic plasticity in a variety of experimental animal models.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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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.

• Science of Emotion and Sensibility
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• v.24 no.2
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• pp.39-48
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• 2021

According to International Associating for the Study of Pain (IASP) definition, neuropathic pain is a disorder characterized by dysfunction of the nervous system that, under normal conditions, mediates virulent information to the central nervous system (CNS). This pain can be divided into a disease with provable lesions in the peripheral or central nervous system and states with an incorporeal lesion of any nerves. Both conditions undergo long-term and chronic processes of change, which can eventually develop into chronic pain syndrome, that is, nervous system is inappropriately adapted and difficult to heal. However, the treatment of neuropathic pain itself is incurable from diagnosis to treatment process, and there is still a lack of notable solutions. Recently, several studies have observed the responses of CNS to harmful stimuli using image analysis technologies, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and optical imaging. These techniques have confirmed that the change in synaptic-plasticity was generated in brain regions which perceive and handle pain information. Furthermore, these techniques helped in understanding the interaction of learning mechanisms and chronic pain, including neuropathic pain. The study aims to describe recent findings that revealed the mechanisms of pathological pain and the structural and functional changes in the brain. Reflecting on the definition of chronic pain and inspecting the latest reports will help develop approaches to alleviate pain.