• Annals of Clinical Neurophysiology
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• v.17 no.1
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• pp.1-16
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• 2015

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

• Annals of Clinical Neurophysiology
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• v.8 no.1
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• pp.63-70
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• 2006

Background: Testosterone is reported to have neuroprotective effect in various neurological diseases. Recently, the mechanism involved in nitric oxide (NO)-mediated motor neuron death is under extensive investigation. The Cu/Zn-superoxide dismutase (SOD1) mutations has been implicated in selective motor neuron death of amyotrophic lateral sclerosis (ALS) and it is said to play an important role in NO-mediated motor neuron death. However, neuroprotective effect of testosterone on motor neuron exposed to NO has rarely been studied. Methods: Motor neuron-neuroblastoma hybrid cells expressing wild-type or mutant (G93A or A4V) SOD gene were treated with $200{\mu}M$ S-nitrosoglutathione. After 24 hr, cell viability was measured by MTT assay. To see the neuroprotective effect of testosterone, pretreatment with 1 nM testosterone was done 1 hr before S-nitroglutathione treatment. To study the mechanism of protective effect, $20{\mu}M$ flutamide (androgen receptor antagonist) was also pretreated with testosterone 1 hr before S-nitroglutathione treatment. Results: S-nitrosoglutathione showed significant neurotoxic effect in all three cell lines. Percentage of cell death was somewhat different in each cell line. 1 nM testosterone showed neuroprotective effect in G93A and wild-type cell line. In A4V cell line, testosterone did not showed neuroprotective effect. The neuroprotective effect of testosterone was reversed by $20{\mu}M$ flutamide. Conclusions: These results indicate that testosterone induces neuroprotection in NO-mediated motor neuron death directly through the androgen receptor. This neuroprotective effect of testosterone varies according to the types of SOD1 gene mutation. These data suggest that testosterone may be of therapeutic value against ALS.

• KSBB Journal
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• v.28 no.5
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• pp.269-274
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• 2013

Motor neuron disease (MND) is a fatal neurodegenerative disorder caused by progressive and selective degeneration of motor neurons (MNs). Because of the versatile nature, stem cells have the potential to repair or replace the degenerated cells. In this review, we discussed stem cell based therapies including the use of embryonic stem cells (ESCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs) and genetically engineered cells to produce the neurotrophic factors for the treatment of MND. To achieve this goal, the knowledge of specificity of the cell target, homing and special markers are required.

• Journal of the Korean Academy of Clinical Electrophysiology
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• v.4 no.1
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• pp.39-47
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• 2006

Functional Electrical Stimulation(FES) cause paralysed muscles to contract in some clinical circumstances. Generally, FES has been thought of as a valuable tool in activating any skeletal muscle paralysed as a result of upper motor neuron damage. But, the function of cardiac and smooth muscle is also affected by upper motor neuron damage. Today, various applications of FES are investigated, including conditioning cardiovascular exercise, caugh and breathing assistant, improving bowel and bladder control, hand grasp, standing and walking etc. This review will focus on the literature reporting application of FES to control respiratory capabilities and internal organ function as well as increase muscular strength, hand grasp, standing and walking in patients with upper motor diseases.

• Annals of Clinical Neurophysiology
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• v.19 no.1
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• pp.34-39
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• 2017

Background: Automated nerve excitability testing is used to assess various peripheral neuropathies and motor neuron diseases. Comparing these excitability parameters with normal data provides information regarding the axonal excitability properties and ion biophysics in diseased axons. This study measured and compared normal values of axonal excitability parameters in both the distal motor and sensory axons of normal Koreans. Methods: The axonal excitability properties of 50 distal median motor axons and 30 distal median sensory axons were measured. An automated nerve excitability test was performed using the QTRACW threshold-tracking software (Institute of Neurology, University College London, London, UK) with the TRONDF multiple excitability recording protocol. Each parameter of stimulus-response curves, threshold electrotonus, current-voltage relationship, and recovery cycle was measured and calculated. Results: Our Korean normal data on axonal excitability showed ranges of values and characteristics similar to previous reports from other countries. We also reaffirmed that there exist characteristic differences in excitability properties between motor and sensory axons: compared to motor axons, sensory axons showed an increased strength-duration time constant, more prominent changes in threshold to hyperpolarizing threshold electrotonus (TE) and less prominent changes in threshold to depolarizing TE, and more prominent refractoriness and less prominent subexcitability and superexcitability. Conclusions: We report normal data on axonal excitability in Koreans. These data can be used to compare various pathological conditions in peripheral nerve axons such as peripheral neuropathies and motor neuron disease.

• Interdisciplinary Bio Central
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• v.4 no.3
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• pp.8.1-8.7
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• 2012

The motor neuron degeneration 2 (mnd2) mice carry a point mutation of A to T nucleotide transversion at the serine 276 residue of high temperature requirement A2 (HtrA2), resulting in losses of an AluI restriction enzyme site (5'AGCT3') and the HtrA2 serine protease activity. Moreover, dysfunctions of HtrA2 are known to be intimately associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Thus, this mnd2 mouse is an invaluable model for understanding the physiological role of HtrA2 and its pathological role in neurodegenerative diseases. Nevertheless, many molecular and cellular biologists in this field have limited experience in working with mutant mouse models due to the necessity of acquired years of the special techniques and knowledges. Herein, using the mnd2 mouse model as an example, we describe easy-to-use standard protocols for web-based analyses of target genes, such as HtrA2, and a novel approach for simple and accurate PCR-AluI-RFLP-based genotype analysis of mnd2 mice. In addition, band resolution of AluI-RFLP fragments was improved in 12% polyacrylamide gel running in 1X Tris-Glycine SDS buffer. Our study indicates that this PCR-AluI-RFLP genotype analysis method can be easily applied by the molecular and cellular biologist to conduct biomedical science studies using the other mutant mouse models.

• International Journal of Oral Biology
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• v.34 no.4
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• pp.177-183
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• 2009

Human mesenchymal stem cell (hMSCs) isolated from human adult bone marrow have self-renewal capacity and can differentiate into multiple cell types in vitro and in vivo. A number of studies have now demonstrated that MSCs can differentiate into various neuronal populations. Due to their autologous characteristics, replacement therapy using MSCs is considered to be safe and does not involve immunological complications. The basic helix-loop-helix (bHLH) transcription factor Olig2 is necessary for the specification of both oligodendrocytes and motor neurons during vertebrate embryogenesis. To develop an efficient method for inducing neuronal differentiation from MSCs, we attempted to optimize the culture conditions and combination with Olig2 gene overexpression. We observed neuron-like morphological changes in the hMSCs under these induction conditions and examined neuronal marker expression in these cells by RTPCR and immunocytochemistry. Our data demonstrate that the combination of Olig2 overexpression and neuron-specific conditioned medium facilitates the neuronal differentiation of hMSCs in vitro. These results will advance the development of an efficient stem cell-mediated cell therapy for human neurodegenerative diseases.

• Journal of Life Science
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• v.32 no.8
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• pp.611-621
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• 2022

Dimethyl sulfoxide (DMSO) is commonly used as control or vehicle solvent in preclinical research of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) due to its ability to dissolve lipophilic compounds and cross the blood brain barrier. However, the biochemical effects of DMSO on the outcomes of preclinical research are often overlooked. In the present study, we investigated whether the long-term oral administration of 5% DMSO affects the neurological, functional, and histological disease phenotype of the copper/zinc superoxide dismutase glycine 93 to alanine mutation (SOD1-G93A) mouse model of amyotrophic lateral sclerosis. SOD1-G93A transgenic mice showed shortened survival time and reduced motor function. We found that administration with DMSO led to increased mean survival time, reduced neurological scores, and improved motor performance tested using the rotarod and grip strength tests. On the other hand, DMSO treatment did not attenuate motor neuron loss in the spinal cord and denervation of neuromuscular junctions in the skeletal muscle. These results suggest that DMSO administration could improve the quality of life of the SOD1-G93A mouse model of ALS without affecting motor neuron denervation. In conclusion, the use of DMSO as control or vehicle solvent in preclinical research may affect the behavioral outcomes in the SOD1-G93A mouse model. The effect of the vehicle should be thoroughly considered when interpreting therapeutic efficacy of candidate drugs in preclinical research.

• YAKHAK HOEJI
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• v.55 no.5
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• pp.385-390
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• 2011

Bee venom (BV), which is extracted from honeybees, has been used in traditional Korean medical therapy. Glutamate-mediated excitotoxicity contributes to neuronal death in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Alzheimer's disease (AD). This study is to investigate the effect of BV on glutamate-induced neurotoxicity on NSC-34 motor neuron cells. To determine the viability of motor neuronal cells, we performed with MTT assays in glutamate-treated NSC-34 cell with BV or without. For the measurement of oxidative stress, DCF assay was used in glutamate-treated NSC-34 motor neuronal cells with BV or without. To investigate the molecular mechanism of BV against glutamate-mediated neurotoxicity in NSC-34 cells, western blot analysis was used. Glutamate significantly decreased cell viability by glutamate dose- or treatment time-dependent manner in NSC-34 cells. However, BV pre-treatment dramatically inhibited glutamate-induced neuronal cell death. Furthermore, we found that BV increased the expression of Bcl-2 protein that is anti-apoptotic protein and reduced the generation of oxidative stress. BV has a neuroprotective role against glutamate neurotoxicity by an increase of anti-apoptotic protein. It suggests that BV may be useful for the reduction of neuronal cell death in neuronal disease models.

• Perspectives in Nursing Science
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• v.2 no.1
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• pp.19-36
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• 2005

Muscle atrophy is defined as a decrease in muscle mass, cross-sectional area, and myofibrillar protein content. Causes inducing muscle atrophy may be inactivity, denervation, undernutrition and steroid. Inactivity may decrease protein synthesis and increase protein breakdown of skeletal muscle. The muscle atrophy due to inactivity was induced by bed rest, hindlimb suspension, cast, total hip replacement arthroplasty, anterior cruciate ligament reconstruction. Denervated atrophy may be induced by the loss of innervation from lower motor neuron. The atrophy was apparent in the lower limb of hemiplegic patients following ischemic stroke and in the hindlimb of ischemic stroke rats. Protein breakdown of skeletal muscle in the undernourished state results in muscle atrophy. The atrophy due to undernutrition was evident in cancer and leukemia patients and in the undernourished rats. Steroids have been used to treat allergies, inflammatory diseases, autoimmune diseases and to inhibit immune function following transplantation. Steroids may induce muscle atrophy by protein breakdown of skeletal muscle. Muscle Physiology Laboratoryat College of Nursing, Seoul National University proved that dexamethasone may induce hindlimb muscle atrophy in rats and exercise and DHEA may attenuate hindlimb muscle atrophy induced by the steroid in rats. Nurses working with patients undergoing steroid treatment need to be cognizant of steroid induced muscle atrophy. They need to assess whether muscle atrophy is being occurred during and after the steroid treatment. Moreover, they need to apply exercise and DHEA to the patients undergoing steroid treatment in order to attenuate the steroid induced muscle atrophy.