1987 Fiscal Year Final Research Report Summary
Pathogenesis and Treatment Strategies of Motor Neuron Diseases as Functions of Retrograde Axoplasmic Transport
| Project/Area Number |
60480219
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
YAMAMOTO Teiji Tohoku University, Associate Professor, 医学部, 助教授 (10106487)
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| Co-Investigator(Kenkyū-buntansha) |
IWASAKI Yuzo Tohoku University, Professor, 医学部, 教授 (00142927)
KONNO Hidehiko Tohoku University, Assistant, 医学部, 助手 (10091688)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Motor neuron disease / Amyotrophic lateral sclerosis / Axoplasmic transport / Lectin / Laminin / Albumin / Immunoglobulin G / レクチン |
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| Research Abstract |
In order to determine the roles of axoplasmic transport in pathogenesis of motor neuron diseases, following studies have been carried out during 1985-1987 period.
1. Role of retrograde axoplasmic transport for survival and death of motor neurons: Although somatic motor neurons are protected by the blood-brain barrier (BBB), their axons and endings distributed widely onto the neuromuscular junctions are exempted from BBB. When Adriamycin, a RNA inhibitor, or ricinus communis agglutinin, an inhibitor of protein synthesis, was injected into the rat sciatic nerve, these substanoes were inoorporated into their soma and within several days to weeks somatic motor neurons contributing to the sciatic nerve underwent selective degeneration. This is thought to be a form of experimental motor neuron disease. The role of retrograde axoplasmic transport for survival of motor neurons is evident from these studies.
2. Retrograde axoplasmic transport of serum proteins into somatic motor neurons: By immun
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ocytochemistry, motor neurons were found normally to inoorporate serum albumin and immunoglobulin G into their cell body by axoplasmic flow from the neuromuscular junction. Albumin binds to diverse substanoes; e.g. a variety of drugs and several metal ions.It is possible therefore that motor neurons might integrate through retrograde axoplasmic flow some neurotoxic substanoes which do not permeate the BBB. Chronic egress of some unknown neurotoxic substanoes via this route might endanger the survival of somatic motor neurons.
3. Retrograde axoplasmic transport of neuromuscular junctional extracellular matrix proteins: Laminin, a component of basement membrane and known to exert a potent neurotrophic activity in vitro, was for the first time demonstrated immunocytochemically in motor neurons. This large glyooprotein, or its fragmant might be an important messenger for motor neurons.
These studies have clearly shown the important roles of retrograde axoplasmic transport in maintenanoe and survival of motor neurons. Conversely, as a future treatment strategy, drug delivery selectively to motor neurons may be achieved circumventing the BBB when the retrograde axoplasmic transport is utilized. Less
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Research Products
(16 results)
