| Co-Investigator(Kenkyū-buntansha) |
KATOH Shinsuke TOTTORI UNIVERSITY, FACULTY OF MEDICINE, NEUROPATHOLOGY, ASSOCIATE PROFESSOR, 医学部・脳研・病理, 助教授 (60194817)
OYANAGI Kiyomitsu TOKYO METROPOLITAN INSTITUTE OF NEUROLOGICAL SCIENCE, NEUROPATHOLOGY, DIRECTOR, 神経病理, 副参事 (00134958)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Amyotrophic lateral sclerosis (ALS) is a disease that selectively and progressively involves upper and lower motor neurons. In spite of proposed several hypotheses about the motoneuron death in this condition, the real pathomechanism is still unknown. In such situation, cytopathological investigation of the motoneurons in autopsied cases of ALS is prerequisite and promising to catch a clue to the cause of this tragic condition. Inclusion bodies that occur in the lower motor neurons are an important cytopathology in this condition. Bunina bodies are small cosinophilic cytoplasmic inclusions that are considered to be spccific of ALS. Hvaline inclusions and skein-like inclusions are both ubiquitinated, indicating that the neurons containing them have the ubiquitin proteolytic system somehow disturbed. In this study, we investigated those inclusions mainly with an EM.. Some of Bunina bodies have many tube-like cisterns among which electron-dense amorphous substance was deposited, exhibitin
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g some similarity to the Golgi apparatus. There were also Bunina bodies that appeared intimately associated with hyaline inclusions, thus raising the possibility that Bunina bodies have heterogeneous origins. Skein-like inclusions, which were bundles of abnormal large filaments, were frequently surrounded to various degrees by a cistern or cisterns, which were considered to be flat primary lysosomes. Hyaline inclusions were a mixture of neurofilaments, abnormal large filaments, and electron dense small granules. Within and near the inclusions, the abnormal filaments often made bundles, exhibiting profiles indistinguishable from those of skein-like inclusions. The hyaline inclusions were often surrounded by autolysosomes too. Montages of neurons containing such hyaline inclusions revealed that the autolysosomes were practically confined to the proximity of the inclusions. These findings indicates that there is some relationship between the two kinds of ubiquitinated inclusions, in spite of an obvious difference of their light microscopical features, and that the two inclusions are both treated, after being ubiquitinated, by lysosomal systems. Less
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