| Project/Area Number |
13670341
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
KATOH Kiyoshi Fukushima Medical University, School of Nursing, Environmental Health, professor, 看護学部, 教授 (40136974)
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| Co-Investigator(Kenkyū-buntansha) |
MASUBUCHI Eiko Fukushima Medical University, 看護学部, 助手 (00315673)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | organophosphorus-induced delayed neurotoxicity / triphenylphosphite / rats / neuronal cell body in the anterior horn / mitochondria / phsophorylated neurofirament / 脊髄前角 / 感受性への加齢の影響 / 軸索終末の減少 / シナプトソーム / コハク酸脱水素酵素活性 |
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| Research Abstract |
At first we tried to produce a convenient rodent model on organophosphrous-induced nerupathy After succeeding to produce triphenylphosphite (TPP)-induced neuropathy in SD rats, we tried to detect anomalously phophorylated neurofilament aggregation in rats with TPP-induced neuropathy ; extending the results of a previous study that demonstrated the phosphorylation of cytosketetal proteins in hens with organophosphorus-induced delayed neuropathy (OPIDN). We also aimed to clarify the effect of TPP on mitochondrial enzyme activity in TPP-induced neuropathy, because mitochondrion thought to be the target of TPP-induced neurotoxicity.
Female SD rats underwent repeated (once a day every other day for three times) dermal administration of 500 mg/kg of TPP. Three days after the final administration, animals were sacrificed for morphological and biochemical observations. Dysfunctional changes characterized by circling behavior, backward gait and hind limb ataxia developed one to two days after th
… More
e final administration. Although, both phosphorylated and non-phosphorylated neurofilament staining showed obvious morphological changes in the axons of TPP-treated rats, anomalously phosphorylated neurofilament aggregations were not revealed. Ultrastructural observation showed destruction of various kind of organelles including mitochondria in the neuronal cell body in the anterior horn of lumbar cord. The mean mitochondrial succinate dehydrogenase activity in the spinal cord of TPP-treated rats was less than a half of that of the control. This observation was also noted in the skeletal muscle mitochondria.
Our findings suggest that neurofilamernt phosphorylation, which is characteristic of OPIDN, dose not contribute to TPP-induced neurotoxicity, that TPP induces neural change via a metabolic mechanism, and that the mitochondrion is the target of TPP-induced delayed neurotoxicity. The mechanism of TPP-induced neurotoxicity seems to be different from that of classical organophosphorus-induced neirotoxicity. Less
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