| Project/Area Number |
12670636
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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 OF MEDICAL RESEARCH |
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Principal Investigator |
WATABE Kazuhiko Tokyo Metropolitan Organization For Medical Research, Molecular Neuropathology, 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) |
KAWANO Hitoshi Tokyo Metropolitan Organlzation for Medical Research, Senior Scientist, 東京都神経科学総合研究所, 副参事研究員 (20161341)
OYANAGI Kiyomitsu Tokyo Metropolitan Organlzation for Medical Research, Neuropathology, Senior Scientist, 東京都神経科学総合研究所, 副参事研究員 (00134958)
OHASHI Toya Jikei Univ. Sch. Med., Gene Therapy, Assoc. Professor, DNA医学研究所, 助教授 (60160595)
SANGO Kazunori Tokyo Metropolitan Organlzation for Medical Research, Senior Scientist, 東京都神経科学総合研究所, 主任研究員 (50291943)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Adenovirus / Avulsion / Facial nerve / Motoneuron / Gene therapy / GDNF / BDNF / TGFβ2 / アデノウイルスベクター(3) / カルジオトロフィン-1 |
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| Research Abstract |
We examined neuroprotective effects of recombinant adenoviral vectors encoding glial cell linederived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT 1), transforming growth factor-β2 (TGFβ2), and insulin-like growth factor-1 (IGF1) on lesioned adult rat facial motoneurons. The right facial nerves of adult Fischer 344 male rats were avulsed and removed from the stylomastoid foramen, and adenoviral vectors were injected into the facial canal. Animals avulsed and treated with adenovirus encoding GDNF, BDNF, CNTF, CT1, TGFβ2 and IGF1 showed intense immunolabeling for these factors in lesioned facial motoneurons, respectively, indicating adenoviral induction of the neurotrophic factors in these neurons. The treatment with adenovirus encoding GDNF, BDNF or TGFβ2 after avulsion significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase immunoreactivity and prevented the induction of nitric oxide synthase activity in these neurons. The treatment with adenovirus encoding CNTF, CT1 or IGF1, however, failed to protect these neurons after avulsion. These results indicate that adenovirus-mediated gene transfer of GDNF and BDNF and TGFβ2 but not CNTF, CT1 or IGF1 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
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