| Co-Investigator(Kenkyū-buntansha) |
ITO Seiji Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (80201325)
NISHIZAWA Mikio Kansai Medical University, Faculty of Medicine, Lecturer, 医学部, 講師 (40192687)
ITO Hidefumi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20250061)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
To clarify the significance of inclusion formation for neurodegeneration in patients with adult-onset atypical motor neuron disease with basophilic inclusions, in the present study we have attempted to analyze constituents of the inclusion. For this purpose, we investigated immunohistochemically the formalin-fixed, paraffin-embedded brain and spinal cord sections obtained from autopsy, using various primary antibodies as follows ; anti-ubiquitin, anti-Abeta, anti-phosphorylated neurofilament, anti-MAP subtypes, anti-actin, anti-vimentin, anti-SOD1, anti-alfa-synuclein, and anti-cystatin C. Unfortunately, most of these primary antibodies had not immunoreacted with the inclusions, except antibodies to ubiquitin and cystatin C, with which the inclusions showed deposits of a granular reaction products. Since cystatin C is a Golgi apparatus-related protein, we had applied antibodies againsto other repaltd proteins, MG160 and trans-Golgi-network, for further investigation. However, these ant
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ibodies had not immunostained the inclusions. On the other hand, the anti-MG160 antibody clearly recognized Golgi apparaatus of normal-looking anterior horn cells in the form of larger, angular, or elongated profiles. In contrast, all neurons bearing the basophilic inclusions showed fragmentation and reduced number of the Golgi apparaatus. These findings were similar to the previously reported observaations in motor neurons of classic ALS patients and of mutant SOD1 transgenic mice.Therefore, our findings suggest that the formation of the basophilic inclusions may not represent a protective reaction for the isolation of harmful products, but may contribute to irreversible neurodegeneration. Furthermore, our results indicate that common pathogenetic mechanisms may be involved in the formation of the basophilic inclusions and in the fragmentation of the Golgi apparatus. In addition, the present observations imply that the adult-onset atypical motor neuron disease with basophilic inclusions, classic ALS and mutant SOD1 transgenic mice may share similar neurodegeneration process, the fragmentation of the Golgi apparatus being as an earlier sign. Less
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