• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.125-137
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• 2013

Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.46-46
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• 2002

Cdk5, a neuronal Cdc2-like kinase, exhibits a variety of functions in neuronal differentiation and neurocytoskeleton dynamics as well as neuronal degeneration and cell death. However, its role in retinoic acid (RA)-induced differentiation has not been reported yet. We newly found that RA treatment of SK-N-BE(2)C, human neuroblastoma, increased expression of Cdk5 concomitantly with a neuronal specific activator, p35.(omitted)

• Journal of the Korea Convergence Society
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• v.7 no.2
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• pp.61-67
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• 2016

The olfactory system is an important model for the study of neuronal degeneration and regeneration, including neuronal diseases. When the olfactory sensory neurons are damaged by nerve injury or are exposed to environmental factors, they degenerate and are replaced by regenerating neurons. To monitor neuronal degeneration in living animal, we established an olfactory-specific GFP transgenic zebrafish. The effects of Triton X-100 or sodium acetate on the olfactory system were examined. A significant decrease in the number of GFP-positive olfactory sensory neurons was observed after chemical lesion. We found a recovery of GFP-positive neurons by 2 days posttreatment. From these results, we expect that further studies of olfactory degeneration and regeneration using this transgenic zebrafish will provide important advances for the study of neuronal degeneration and regeneration.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.1
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• pp.51-58
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• 2015

Ethanol has long been implicated in triggering apoptotic neurodegeneration. Alcohol also may indirectly harm the fetus by imparing the mother's physiology. We examined the effects of ethanol on immature brain of mice. Three-weeks-old female ICR strain mice daily intraperitoneally injected with ethanol at the concentration of 4 and 20% in saline for 0, 6, and 24 hours and 1 and 4 weeks. The mice were weighted and sacrificed, and the brains were ectomized for the present histological, immunohistochemical and TUNEL assays. Based on the histologic hematoxylin and eosin stain, immunohistochemical expression of glutamate receptor protein and neuronal cell adhesion molecule (NCAM) were evaluated. The cerebral cortex of the ethanol-treated group showed few typical symptoms of apoptosis such as chromosome condensation and disintegration of the cell bodies. TUNEL staining revealed DNA fragmentation in the 6 and 24 hours. This results demonstrated that acute ethanol administration causes neuronal cell death. I found that either glutamate receptor inhibition or activation could induce cerebellar degeneration as ethanol effect. Neuronal death also can be induced by excess activity of certain neurotransmitter, including glutamate. Neurons must establish cell-to-cell contact during growth and development in order to survive, migrate to their final destination, and develop appropriate connections with neighboring cell. Purkinje cell in cerebellar are especially vulnerable to the cell death and degeneration. After ethanol treatment in cerebellar, NCAM had decreased by 4 weeks. This result suggest that apoptosis seems to be involved in the slow elimination of neuron and cerebellar degeneration.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.289-297
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• 1996

Excitatory amino acids (EAA) are thought to play an important role in producing cell death associated with ischemic and traumatic spinal cord injury. The present study was carried out to determine if the response characteristics of spinal sensory neurons in segments adjacent to degeneration sites induced by EAA are altered following these morphological changes. Intraspinal injections of quisqualic acid (QA) produced neuronal degeneration and spinal cavitation of gray matter. The severity of lesions was significantly attenuated by pretreatment with a non-NMDA antagonist NBQX. In extracellular single unit recordings, dorsal horn neurons in QA injected animal showed the increased mechanosensitivity, which included a shift to the left in the stimulus-response relationship, an increased background activity and an increase in the duration of after-discharge responses. Neuronal responses, especially the C-fiber response, to suprathreshold electrical stimulation of sciatic nerve also increased in most cases. These results suggest that altered functional states of neurons may be responsible for sensory abnormalities, e.g. allodynia and hyperalgesia, associated with syringomyolia and spinal cord injury.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.55-63
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• 2000

Soeumin Sibjeundaibo-tang (SJDBT) and Soyangin Sibimijihwang-tang (SMJHT) have been used traditionally to improve the systemic blood circulation and biological energy production in the patients with circulatory and neuronal diseases. The object of this study is to determine the protective effects of SJDBT and SMJHT extracts on the spontaneous and glutamate-induced neuronal damages in cultured cells derived from mice cerebral cortex. At 14 days after beginning the cultures, the activity of lactate dehydrogenase released into the culture media was significantly decreased by treatment of cerebroneuronal cells with SJDBT and SMJHT (0.1 mg/ml) for 7 days. By comparison with the normal cells, cerebroneuronal morphology was dramatically changed by treatment of glutamate (1 mM) for 12 hrs, and this was conspicuously recovered by pretreatment of cerebroneural cells with SJDBT and SMJHT (0.1-1.0 mg/ml) for 2 days. Moreover, glutamated-induced DNA fragmentation was also protected by pretreatment of cerebroneuronal cells with those extracts. These results suggest that naturally occurring and glutamate-induced degeneration of cultured cerebrocortical cells may be related, in part, to the process of apoptotic cell death. The pharmacological properties of SJDBT and SMJHT extracts to improve cerebroneuronal degeneration may be considered as one of useful medicines that can prevent cerebrocortical impairments resulted from age-dependent and excitotoxicity-induced neuronal degeneration in human brain.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.21-30
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• 1998

Ginseng root has been considered to prevent neuronal degeneration associated with brain ischemia, but experimental proof in support of this speculation is limited. Moreover, few studies have compared the neuroprotective actions of ginseng ingredients with those of peptide growth factors and cytokines isf vivo. Using a gerbil forebrain ischemia model, we demonstrated that the oral administration of red ginseng powder before an ischemic insult prevents delayed neuronal death in the hippocampal CAI field and that a neuroprotective molecule within red ginseng powder is ginsenoside Rbl. The neurotrophic effect of ginsenoside Rbl, when examined in the gerbil ischemia model and in neuronal cultures was as potent as or more potent than the effects of epidermal growth factor, ciliary neurotrophic factor, erythropoietin, prosaposin, interleukin-6 and interleukin-3. Besides the protection of hippocampal CAI neurons against brain ischemia/repercussion injuries, ginsenoside Rbl was shown to prevent place navigation disability, cortical infarction and secondary thalamic degeneration in stroke-prone spontaneous hypertensive rats with permanent occlusion of the unilateral middle cerebral artery distal to the striate branches. These findings may validate the empirical use of ginseng root for the treatment of cerebrovascular diseases

• Journal of Korean Neurosurgical Society
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• v.38 no.4
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

• Molecules and Cells
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• v.45 no.11
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• pp.846-854
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• 2022

Neurons make long-distance connections via their axons, and the accuracy and stability of these connections are crucial for brain function. Research using various animal models showed that the molecular and cellular mechanisms underlying the assembly and maintenance of neuronal circuitry are highly conserved in vertebrates. Therefore, to gain a deeper understanding of brain development and maintenance, an efficient vertebrate model is required, where the axons of a defined neuronal cell type can be genetically manipulated and selectively visualized in vivo. Placental mammals pose an experimental challenge, as time-consuming breeding of genetically modified animals is required due to their in utero development. Xenopus laevis, the most commonly used amphibian model, offers comparative advantages, since their embryos ex utero during which embryological manipulations can be performed. However, the tetraploidy of the X. laevis genome makes them not ideal for genetic studies. Here, we use Xenopus tropicalis, a diploid amphibian species, to visualize axonal pathfinding and degeneration of a single central nervous system neuronal cell type, the retinal ganglion cell (RGC). First, we show that RGC axons follow the developmental trajectory previously described in X. laevis with a slightly different timeline. Second, we demonstrate that co-electroporation of DNA and/or oligonucleotides enables the visualization of gene function-altered RGC axons in an intact brain. Finally, using this method, we show that the axon-autonomous, Sarm1-dependent axon destruction program operates in X. tropicalis. Taken together, the present study demonstrates that the visual system of X. tropicalis is a highly efficient model to identify new molecular mechanisms underlying axon guidance and survival.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.1-15
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• 2010

Objectives : This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFS) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results : 1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions : These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration. following SCI.