• Korean Journal of Veterinary Research
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• v.38 no.2
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• pp.290-296
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• 1998

Histological changes was investigated in the 4 weeks old rat brain using NMDA (N-methyl-D-asparate) which is capable of mediating excitotoxic events. The changes were occured when the injected NMDA solved in PBS was over $1.0{\mu}g/g$(about 90nM). The necrosis of Purkinje cells in cerebellum and the increasement of coloidal plexus cell number were prevalent. The Purkinje cell number of necrosis were increased according to increasement of amount of injected NMDA. In spite of increasement of degenerated Purkinje cell number, differentiation of new Purkinje cell was not identified because total number of Purkinje cell was not changed. The change of cell number was observed in coloidal plexus cell rather than degeneration of cell. About 5 time increasement was occured. This change may cause increasement of cerebrospinal fluid and the makes mophorogy of brain more round than nomal.

• Molecules and Cells
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• v.20 no.2
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• pp.219-227
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• 2005

Purkinje cell degeneration (pcd) mice are characterized by death of virtually all cerebellar Purkinje cells by postnatal day 30. In this study, we used DNA microarray analysis to investigate differences in gene expression between the brains of wild type and pcd mice on postnatal day 20, before the appearance of clear-cut phenotypic abnormalities. We identified 300 differentially expressed genes, most of which were involved in metabolic and physiological processes. Among the differentially expressed genes were several calcium binding proteins including calbindin-28k, paravalbumin, matrix gamma-carboxyglutamate protein and synaptotagamins 1 and 13, suggesting the involvement of abnormal $Ca^{2+}$ signaling in the pcd phenotype.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.164-173
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• 2000

This study was carried out to investigate the direct neurotoxicity of alcohol on CNS and the effects of piracetam or vitamins on ultrastructural changes of the rat cerebellar and hippocampal neurons during long-term alcohol treatment. To evaluate the results, quantitative analysis were done for light and electronic microscopic findings. On the light microscopy, red degeneration of pyramidal cells and Purkinje cells was found more apparently in the alcohol only treated group than in the control group. On the electron microscopy, increased lipofuscin pigments were found in cerebellum and hippocampus. In quantitative analysis, vitamins significantly reduced red degeneration in both hippocampus and cerebellum. However, piracetam significantly reduced red degeneration in cerebellum but not in hippocampus. Lipofuscin pigments in Purkinje cells and pyramidal cells were significantly reduced in the alcohol with piracetam treated group than the alcohol only treated group. However, vitamins had no significant reducing effect of lipofuscin pigments in Purkinje cells and pyramidal cells. According to the results, it is concluded that vitamins deficiency might cause red degeneration of pyramidal cell after long-term alcohol treatment, but increment of lipofuscin pigments in pyramidal and Purkinje cell may be caused by alcohol itself or its metabolite rather than vitamins deficiency. Piracetam seems to improve cognitive function impairment caused by alcohol consumption.

• 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 and Pharmacology
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• v.13 no.5
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• pp.373-378
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• 2009

Cerebellar Purkinje cells (PCs) play a crucial role in motor functions and their progressive degeneration is closely associated with spinocerebellar ataxias. Although immunohistochemical (IHC) analysis can provide a valuable tool for understanding the pathophysiology of PC disorders, the method validation of IHC analysis with cerebellar tissue specimens is unclear. Here we present an optimized and validated IHC method using antibodies to calbindin D28k, a specific PC marker in the cerebellum. To achieve the desired sensitivity, specificity, and reproducibility, we modified IHC analysis procedures for cerebellar tissues. We found that the sensitivity of staining varies depending on the commercial source of primary antibody. In addition, we showed that a biotin-free signal amplification method using a horseradish peroxidase polymer-conjugated secondary antibody increases both the sensitivity and specificity of ICH analysis. Furthermore, we demonstrated that dye filtration using a $0.22\;{\mu}m$ filter eliminates or minimizes nonspecific staining while preserving the analytical sensitivity. These results suggest that our protocol can be adapted for future investigations aiming to understand the pathophysiology of cerebellar PC disorders and to evaluate the efficacy of therapeutic strategies for treating' these diseases.

• Applied Microscopy
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• v.35 no.3
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• pp.165-176
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• 2005

Studies on molecular plasticity of Bermann glia (BG) after harmaline-induced Purkinje cell (PC) degeneration in the rat cerebellum. The intimate structural relationship between BG and PC, evidenced by the sheathing of the PC dendrites by veil-like process from the BG has been suggestive of the close functional relationship between these two cell types. However, little is known about metabolic couplings between these cells. This study designed to investigate molecular plasticity of BG in the rat cerebellum in which PCs were chemically ablated by harmaline treatment. Immunohistochemical examination reveals that harmaline induced PC degeneration causes a marked glial reaction in the cerebellum with activated BG and microglia aligned in parasagittal stripes within the vermis. In these strips, activated BG were associated with upregulaion of metallotheionein, while GLAST and was down regulated, as compared with nearby intact area where both BG are in contact with PCs. The data from this study demonstrate that BG can change their phenotypic expression when BG loose their contact with PCs. It is conceivable that activated BG may upregulate structural proteins, metallothionein expression to use for their proliferation and hypertrophy; metallothionein expression to cope with oxidative stress induced by PC degeneration and microglial activation. On the contrary, BG may down regulated expression of GLAST because sustained loss of contact with PCs would eliminate the necessity for the cellular machinery involved glutamate metabolism. In conclusion, BG might respond man to death of PCs by undergoing a change in metabolic state. It seems possible that signaling molecules released from PCs regulates the phenotype expression of BG. Also ultrastructures in the organelles of normal PC and BG are distinguished by mitochondrial appearance, and distributed vesicles at the synaptic area in the cytoplasm.

• Journal of International Academy of Physical Therapy Research
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• v.1 no.2
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• pp.91-98
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• 2010

This study is intended to examine the motor skill learning and treadmill exercise on motor performance and synaptic plasticity in the cerebellar injured rats by harmaline. Experiment groups were divided into four groups and assigned 15 rats to each group. Group I was a normal control group(induced by saline); Group II was a experimental control group(cerebellar injured by harmaline); Group III was a group of motor skill learning after cerebellar injured by harmaline; Group IV was a group of treadmill exercise after cerebellar injured by harmaline. In motor performance test, the outcome of group II was significantly lower than the group III, IV(especially group III)(p<.001). In histological finding, the experimental groups were destroy of dendrities and nucleus of cerebellar neurons. Group III, IV were decreased in degeneration of cerebellar neurons(especially group III). In immunohistochemistric response of synaptophysin in cerebellar cortex, experimental groups were decreased than group I. Group III's expression of synaptophysin was more increased than group II, IV. In electron microscopy finding, the experimental groups were degenerated of Purkinje cell. These result suggest that improved motor performance by motor skill learning after harmaline induced is associated with dynamically altered expression of synaptophysin in cerebellar cortex and that is related with synaptic plasticity.

• Journal of the Korean Society of Physical Medicine
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• v.5 no.3
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• pp.455-465
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• 2010

Purpose : This study is intended to examine the motor skill learning on balance and coordination in the cerebellar injured rats by 3AP. Methods : This study selected 60 Sprague-Dawley rats of 8 weeks. Experiment groups were divided into four groups and assigned 15 rats to each group. Group I was a normal control group(induced by saline); Group II was a experimental control group(cerebellar injured by 3AP); Group III was a group of motor skill learning after cerebellar injured by 3AP; Group IV was a group of treadmill exercise after cerebellar injured by 3AP. In each group, motor performance test, histologic observations, synaptophysin expression and electron microscopy observation were analyzed. Results : In motor performance test, the outcome of group II was significantly lower than the group III, IV(especially group III)(p<.001). In histological finding, the experimental groups were destroy of dendrities and nucleus of cerebellar neurons. Group III, IV were decreased in degeneration of cerebellar neurons(especially group III). In immunohistochemistric response of synaptophysin in cerebellar cortex, experimental groups were decreased than group I. Group III's expression of synaptophysin was more increased than group II, IV. In electron microscopy finding, the experimental groups were degenerated of Purkinje cell. Conclusion : These result suggest that improved motor performance by motor skill learning after harmaline induced is associated with dynamically altered expression of synaptophysin in cerebellar cortex and that is related with synaptic plasticity.

• Journal of Veterinary Clinics
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• v.11 no.1
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• pp.485-505
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• 1994

Lead toxicity was evaluated in forty-five cats on a balanced diet, treated with 0(control), 10, 100(low), 1, 000, 2, 000 and 4, 000(high)ppm of lead acetate orally on a body weight basis. The objectives were to describe the gross and histopathologic changes and to demonstrate what tissue lead concentrations correlate with the known dosages of lead. In subclinical lead toxicity, greater than 80% of the absorbed lead was deposited in the bone, whereas in more acute lead toxicity, 42% of absorbed lead was deposited in the bone and 36% and 20% of absorbed lead was deposited in the kidneys and in the liver, respectively. No gross lesions were found in the nervous system. Yellow-brown colored livers appear to be associated with lead toxicity. Neuronal necrosis in the cerebrum was the most predominant histopathologic finding. Astrocytic proliferation in the cerebral gray matter was observed in 1 high dose cat. Gliosis was noted in the cerebral cortex of 6 high dose cats. Two high dose cats had demyelination in the deepest layer of the cortical gray matter of the cerebrum. Extravasation of red cells and cavitation around the vessels were found in the cerebrum of 1 high dose cat. Six high dose cats had degeneration of Purkinje cells in the cerebellum. The microscopic findings in the peripheral nerves were ambiguous. In more acute toxicity, the cats had lead inclusions in the epithelial cells of proximal tubules of the kidneys of 7 cats and hepatocytes of the liver of S cats. These inclusions could be seen wlth H&E, but were more prominent with orcein staining. Two high dose cats had granulomas and connective tissue hyperplasia between tubules of the kidneys. Periportal hepatocyte vacuolization was observed in the liver of 22 cats. Vacuolization of seminiferous tubules and a reduced number of spermatogonia(indicative of reduced spermatogenesis) were found in the testis of 5 treated cats. Cystic ovaries were observed in 3 high dose cats and poor development of oogonia was found in 2 cats. The diagnosis of lead toxicity in cats can be suspected on the basis of the histopathologic lesions described, and can be of value in contributing to a diagnosis. A reliable diagnosis of lead poisoning can be helped utilizing tissue lead analysis(post molten)