| Project/Area Number |
14570627
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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 |
Neurology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
WATABE Kazuhiko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Senior Scientist, 東京都神経科学総合研究所, 副参事研究員 (30240477)
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| Co-Investigator(Kenkyū-buntansha) |
OYANAGI Kiyomitsu Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Senior Scientist, 東京都神経科学総合研究所, 参事研究員 (00134958)
KAWAZOE Yoko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Research Scientist, 東京都神経科学総合研究所, 研究員 (60281705)
OHASHI Toya Jikei University School of Medicine, Institute of DNA Medicine, Associate Professor, DNA医学研究所, 助教授 (60160595)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Adenovirus vector / Avulsion / Facial nerve / Motoneuron / Neurotrophic factor / ALS / Schwann cell / SOD1 |
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| Research Abstract |
We have utilized adult rat peripheral nerve avulsion models to evaluate the effects of neuroprotective molecules on motoneuron degeneration. The right facial nerves of adult Fischer 344 male rats were avulsed and adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), transforming growth factor-β2 (TGFβ2), and growth inhibitory factor (GIF) were injected into the facial canal. The treatment with the vectors significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase (ChAT) immunoreactivity and suppressed the induction of nitric oxide synthase activity in these neurons. In separate experiments, animals were orally administered solution of a neuroprotective compound T-588 after avulsion. Both free oral administration and oral tube administration of T-588 improved the survival of injured motoneurons and ameliorated their ChAT immunoreactivity. These results indicate that the gene transfer of GDNF, BDNF, TGFβ2, and GIF and oral administration of T-588 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
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