• The Korean Journal of Pain
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• v.35 no.4
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• pp.391-402
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• 2022

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.

• Molecules and Cells
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• v.21 no.1
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• pp.76-81
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• 2006

Tubulin is synthesized in the cell body and must be delivered to the axon to support axonal growth. However, the exact form in which these proteins, in particular tubulin, move within the axon remains contentious. According to the "polymer transport model", tubulin is transported in the form of microtubules. In an alternative hypothesis, the "short oligomer transport model", tubulin is added to existing, stationary microtubules along the axon. In this study, we measured the translocation of microtubule plus ends in soma segments, the middle of axonal shafts and the growth cone areas, by expressing GFP-EB3 in cultured Xenopus embryonic spinal neurons. We found that none of the microtubules in the three compartments were transported rapidly as would be expected from the polymer transport model. These results suggest that microtubules are stationary in most segments of the axon, thus supporting the model according to which tubulin is transported in nonpolymeric form in rapidly growing Xenopus neurons.

• The Journal of Korean Medicine
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• v.29 no.2
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• pp.133-150
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• 2008

Objective: This study was performed to examine Danggui (DG, Angelica gigas Nakai)'s potential activity for promoting axonal regeneration in the injured peripheral nerve. Methods: Using the sciatic nerve in the rats, DG extract 5 ${\mu}l$(10 mg/ml in 0.5% saline) was dripped into the injury site of the nerve. Results: DG treatment facilitated axonal elongation responses in the distal portion to the injury site. GAP-43 protein levels were upregulated by DG treatment in the injured nerve and also in the DRG, suggesting the induction of GAP-43 expression at gene expression level after nerve injury. Phospho-Erk1/2 protein levels were upregulated in the injured nerve area and also in the DRG, suggesting retrograde transport of phospho-Erk1/2 protein from the injury area to the cell body. Cdc2 protein levels were slightly upregulated by DG treatment. DG treatment increased the number of non-neuronal cells in the distal portion to the injury site. Conclusions: The present data suggest that DG is effective for enhanced axonal regrowth after sciatic nerve injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.431-437
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• 2008

Sengmaek-san(Shengmai-san; SMS) is used in oriental medicine as one of the key herbal medicine for treating diverse symptoms including cardiovascular and neurological disorders. In the present study, the effects of SMS on axonal regeneration were investigated in the rat model given sciatic nerve injury. SMS treatment enhanced axonal regrowth into and the number of non-neuronal cells in the distal area after crush injury. GAP-43 protein levels were increased in the injured sciatic nerve compared to intact nerve and further upreguated by SMS treatment. GAP-43 protein was increased similarly in the dorsal root ganglion (DRG) at lumbar 4 - 6 by nerve injury and SMS treatment, suggesting GAP-43 induction at gene expression level. SMS-mediated increase in phospho-Erk1/2 protein was observed in the DRG as well as in the injured nerve implying its retrograde transport into the cell body as the process of lesion signal transmission. The present findings suggest that SMS may be involved in enhanced axonal regeneration via dynamic regulation of regeneration-associated proteins.

• BMB Reports
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• v.48 no.3
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• pp.139-146
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• 2015

Adaptive brain function and synaptic plasticity rely on dynamic regulation of local proteome. One way for the neuron to introduce new proteins to the axon terminal is to transport those from the cell body, which had long been thought as the only source of axonal proteins. Another way, which is the topic of this review, is synthesizing proteins on site by local mRNA translation. Recent evidence indicates that the axon stores a reservoir of translationally silent mRNAs and regulates their expression solely by translational control. Different stimuli to axons, such as guidance cues, growth factors, and nerve injury, promote translation of selective mRNAs, a process required for the axon's ability to respond to these cues. One of the critical questions in the field of axonal protein synthesis is how mRNA-specific local translation is regulated by extracellular cues. Here, we review current experimental techniques that can be used to answer this question. Furthermore, we discuss how new technologies can help us understand what biological processes are regulated by axonal protein synthesis in vivo.

• Korean Journal of Veterinary Research
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• v.52 no.2
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• pp.99-104
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• 2012

The present study was performed to evaluate the relationship between the neurotoxicity of acrylamide and the differential gene expression pattern in mice. Both locomotor test and rota-rod test showed that the group treated with higher than 30 mg/kg/day of acrylamide caused impaired motor activity in mice. Based on cDNA microarray analysis of mouse brain, myelin basic protein gene, kinesin family member 5B gene, and fibroblast growth factor (FGF) 1 and its receptor genes were down-regulated by acrylamide. The genes are known to be essential for neurofilament synthesis, axonal transport, and neuroprotection, respectively. Interestingly, both FGF 1 and its receptor genes were down-regulated. Genes involved in nucleic acid binding such as AU RNA binding protein/enoyl-coA hydratase, translation initiation factor (TIF) 2 alpha kinase 4, activating transcription factor 2, and U2AF 1 related sequence 1 genes were down-regulated. More interesting finding was that genes of both catalytic and regulatory subunit of protein phosphatases which are important for signal transduction pathways were down-regulated. Here, we propose that acrylamide induces neurotoxicity by regulation of genes associated with neurofilament synthesis, axonal transport, neuro-protection, and signal transduction pathways.

• The Journal of Korean Physical Therapy
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• v.15 no.2
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• pp.67-74
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• 2003

Nervous system is clinically important, and involved in most disorders directly or indirectly. It could be injury and be a source of symptoms. Injury of central or peripheral nervous system injury may affect that mechanism and interrupt normal function. An understanding of the concepts of axonal transport is important for physical therapist who treat injury of nerves. Three connective tissue layers are the endoneurium, perineurium, epineurium. Each has its own special structural characteristics and functional properties. The blood supply to the nervous system is well equipped in all dynamic and static postures with intrinsic and extrinsic vasculation. After nerve injury, alternations in the ionic compression or pressures within this environment may interfere with blood flow and, consequently conduction and the flow of axoplasm. The cytoskeleton are not static. On the contrary, elements of the cytoskeleton are dynamically regulated and are very likely in continual motion. It permits neural mobility. There are different axonal transport systems within a single axon, of which two main flows have been identified : First, anterograde transport system, Secondly, retrograde transport system. The nervous system adapts lengthening in two basic ways. The one is that the development of tension or increased pressure within the tissues, increased intradural pressure. The other is movements that are gross movement and movement occurring intraneurally between the connective tissues and the neural tissues. In this article, we emphasize the biologic aspects of nervous system that influenced by therapeutic approaches. Although identified scientific information in basic science is utilized at clinic, we would attain the more therapeutic effects and develop the physical therapy science.

• Journal of Environmental Health Sciences
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• v.22 no.3
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• pp.8-16
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• 1996

Effects of water extract of aloe vera on lead-induced neurotoxicity were investigated in sciatic nerve isolated from rat. The mechanism on toxicity reduction by measuring activities of axonal enzymes, metabolism of myo-inositol in nerve, lead concentration in several organs and so on were further examimed. In the lead-treated rats, the transport rate of axonal enzyme, such as acetyl cholinesterase and choline acetyltransferase, was reduced by from 50% to 30% respectively. Reduction in myo-inositol concentration and $Na^+/K^+$ ATPase activity were also observed in sciatic nerve from lead-treated rat. However, the aloe extract administration significantly eliminated the impairment and maintained myo-inositol concentration to about 85% of normal level. Also aloe extract promoted the excretion rate of lead which is accumulated in blood, sciatic nerve and kidney. These results suggest that lead-induced neurotoxicity was significantly reduced by administration of aloe extract and the mechanism might be partly increase in kidney excretion rate of lead and parity normalization of $Na^+/K^+$ ATPase activity which is critical factor in order to keep nerve maintaining normal myo-inositol level.

• BMB Reports
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• v.56 no.3
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• pp.178-183
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• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• Journal of environmental and Sanitary engineering
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• v.10 no.3
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• pp.45-55
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• 1995

This study was carried out to elucidate the toxic mechanism of cadmium in peripheral nerve. An animal model of cadmium neuropathy was induced by feeding diet containing cadmium to Sprague- Dawley rat (or two weeks. Four weeks aged Sprague- Dawley rats were divided into four groups : normal control group, 10ppm- cadmium treated group, 100ppm- cadmium treated group, 1000ppm- cadmium treated group, reference drug- treated group. All rats were sacrificed at the end of two weeks for assessing the development of cadmium neuropathy, These results obtained were summarized as follows : 1. Cadmium reduced peripheral flow of both acetylcholinesterase and cholinesterase in rat sciatic nerve. 2. The toxic mechanism of cadmium might be the result of an reduction of myo-inositol concentration in peripheral nervous system 3. Reduction in myo-inositol content of peripheral nerve resulted from the inhibition of sodium- Potassium ATPase activity, which is responsible for myo-inositol transport, by cadmium 4. Oral administration of myo-inositol improved the flow of both acetylcholinesterase and cholinesterasenerve in cadmium intoxicated rat. These results suggest that mild cadmium neuropathy might be diagnosed by checking nervous myo-inositol content and oral administraion of myo-inositol might prevent the development of severe cadmium neuropathy with special reference to detective axonal transport.