2006 Fiscal Year Final Research Report Summary
Anti-apoptotic Therapy (Intrathecal Injection of Anti-apoptotic PTD-FNK Protein) in a Mouse Model of Amyotrophic Lateral Sclerosis
| Project/Area Number |
17590879
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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 | Okayama University |
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Principal Investigator |
TAKEHISA Yasushi Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (00379752)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Koji Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (20212540)
NAGAI Makiko Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (80420488)
HAYASHI Takeshi Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (40314679)
MURAKAMI Tetsuro Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (70403475)
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| Project Period (FY) |
2005 – 2006
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| Keywords | ALS / ant-apoptotic therapy / neural precursor cell / IGF-1 / neurotrophic factors / FNK / intrathecal infusion / SODG93A transgenic mice |
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| Research Abstract |
We investigated three steps of neural precursor cell activation-proliferation, migration, and differentiation.in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide disniutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule.1 (Ibal), BrdU + glial fibrillary acidic protein (GFAP). or BrdU + highly polysialylated neural cell adhesion molecule (.PSA-NCAM.) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns. which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.
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Research Products
(8 results)
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[Journal Article] PINK1, a gene product of PARK6, accumulates in □-synucleinopathy brains.2007
Author(s)
Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta, Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe
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Journal Title
J Neurol Neurosurg Psychiatry. 8(Epub ahead of prin)
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation- associated familial amyotrophic lateral sclerosis and its transgenic mouse model.2007
Author(s)
Shibata N, Kawaguchi M, Uchida K, Kakita A, Takahashi H, Nakano R, Fujimura H, Sakoda S, Ihara Y, Nobukuni K, Takehisa Y, Kuroda S, Kokubo Y, Kuzuhara S, Honma T, Mochizuki Y, Mizutani T, Yamada S, Toi S, Sasaki S, Iwata M, Hirano A, Yamamoto T, Kato Y, Sawada T, Kobayashi M
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Journal Title
Neuropathology. 27
Pages: 49-61
Description
「研究成果報告書概要(和文)」より
-
[Journal Article] PINK1, a gene product of PARK6, accumulates in □-synucleinopathy brains.2007
Author(s)
Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe
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Journal Title
J Neurol Neurosurg Psychiatry. 8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model.2007
Author(s)
Shibata N, Kawaguchi M, Uchida K, Kakita A, Takahashi H, Nakano R, Fujimura H, Sakoda S, Ihara Y, Nobukuni K, Takehisa Y, Kuroda S, Kokubo Y, Kuzuhara S, Honma T, Mochizuki Y, Mizutani T, Yamada S, Toi S, Sasaki S, Iwata M, Hirano A, Yamamoto T, Kato Y, Sawada T, Kobayashi M.
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Journal Title
Neuropathology. 27
Pages: 49-61
Description
「研究成果報告書概要(欧文)」より
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