2007 Fiscal Year Final Research Report Summary
Amelioration of spinal cord injury by the regulation of neurotmphin receptor p75-mediated signaling
| Project/Area Number |
18390420
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
FURUKAWA Shoei Gifu Pharmaceutical University, Faculty of Pharmaceutical Science, Professor (90159129)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMITSU Hidefumi Gifu Pharmaceutical University, Faculty of Pharmaceutical Science, Assistant Professor (00308280)
NOMOTO Hiroshi Gifu Pharmaceutical University, Faculty of Pharmaceutical Science, Associate Professor (80164747)
FURUKAWA Yoshiko Matsuyama University, Faculty of Pharmaceutical Science, Professor (20219108)
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| Project Period (FY) |
2006 – 2007
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| Keywords | p75NTR / neurotronhin recentor / spinal cord injury / apoptosis / genetically modified animal / recovery of locomotion activity / nerve growth factor / brain-derived neurotrophic factor |
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| Research Abstract |
1. Analysis of alteration of gene expression after spinal cord injury
Genes of which expression were altered in the injured spinal cord were analyzed by the DNA array method. The 46 genes including inflammatory cytokines or lymphokines were upregulated and 18 genes involving ion transporter or amino acid transporter were downregulated. We focused on and analyzed some genes related to p75NTR signaling.
2 Evaluation of the peptides that suppress the p75NTR-induced negative signals.
a) A peptide expected to inhibit the binding between RhoGDI and p75, and b) the peptide expected to inhibit the binding between sortilin and pro-brain-derived neurotrophic factor (BDNF) were examined their activities on the locomotion activity after spinal cord injury. However, both peptides failed to improve the locomotion activity. Various proteases induced in the injury site of the spinal cord may be responsible for the degradation of the peptides.
3 Amelioration of the spinal cord injury in p75NTR gene-modifie
… More
d animals
The improvement of locomotion activity after spinal cord injury was compared between p75NTR gene-disrupted mouse (KO mouse) and wild mouse. KO mouse gave higher scores of the locomotion activity than wild mouse for the first 8 days, but the difference was disappeared thereinafter, suggesting that p75NTR signal disturbs the restoration at early stages of the damage.
4 Development of the conditional p75NTR transgenic (Tg) mouse
The vector DNA containing a stop codon between loxp genes and the p75NTR gene in the down stream was constructed, and transferred to fertilized eggs. Because the introduced p75NTR gene does not express as long as stop codon between loxp is not deleted, the maintenance of the animal is easy. If the transgenic mice expressing cre enzyme gene in a region-specicic manner were hybridized with this p75NTR Tg mouse, the p75NTR gene would express simultaneously in the cre enzyme expressing regions. This Tg animals would become useful tool to investigate p75NTR function in the future. Less
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[Journal Article] Adenovirus-mediated retrograde transfer of neurotrophin-3 gene enhances survival of anterior horn neurons of twy/twy mice with chronic mechanical compression of the spinal cord.-2008
Author(s)
Uchida, K, Nakajima, H, Inukai, T, Takamura, T, Kobayashi, S, Furukawa, S, Baba, H
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Journal Title
J Neurosci Res 86
Pages: 1789-1800
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ebselen, a redox regulator containing a selenium atom, induces neurofilament M expression in cultured rat pheochromocytoma PC12 cells via activation of mitogen-activated protein kinase.2008
Author(s)
Nishina, A, Sekiguchi, A, He, Y, Koketsu, M, Furukawa, S
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Journal Title
J Neurosci Res 86
Pages: 720-725
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Selenazoles (selenium compounds) facilitate survival of cultured rat pheochromocytoma PC12 cells after serum-deprivation and stimulate their neuronal differentiation via activation of Akt and mitogen-activated protein kinase, respectively2007
Author(s)
Nishina, A, Sekiguchi, A, Fukumoto, R, Koketsu, M, Furukawa, S
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Journal Title
Biochem Biophys Res Commun 352
Pages: 360-365
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro.2007
Author(s)
Hattori, N, Nomoto, H, Fukumitsu, H, Mishima, S, Furukawa, S
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Journal Title
Biomed Res 28
Pages: 261-266
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] AMP N_1-oxide, a unique compound of royal jelly, induces neurite outgrowth from PC12 cells via signaling by protein kinase A independent of that by mitogen-activated protein kinase2007
Author(s)
Hattori, N, Nomoto, H, Fukumitsu, H, Mishima, S, Furukawa, S
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Journal Title
Evid Based Complement Altern Med, Advance Access published on October 29
Description
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[Journal Article] An analog of a dipeptide-like structure of FK506 increases glial cell line-derived neurotrophic factor expression through cAMP response element-binding protein activated by heat shock protein 90/Akt signaling pathway2006
Author(s)
Cen X, Nitta A, Ohya S, Zhao Y, Ozawa N, Mouri A, Wang L, Suzuki M, Saito K, Ito Y, Kawagoe T, Noda Y, Ito Y, Furukawa S, Nabesbima T
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Journal Title
J Neurosci 26
Pages: 3335-3344
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] An analog of a dipeptide-like structure of FK506 increases glial cell line-derived neurotrophic factor expression through cAMP response element-binding protein activated by heat shock protein 90/Akt signaling pathway.2006
Author(s)
Cen, X, Nitta, A, Ohya, S, Zhao, Y, Ozawa, N, Mouri, A, Wang, L, Suzuki ,M, Saito, K, Ito, Y, Kawagoe, T, Noda, Y, Ito, Y, Furukawa, S, Nabeshima, T
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Journal Title
J Neurosci 26
Pages: 3335-3344
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Autocrine activation of cultured macrophages by brain-derived neurotrophic factor.2006
Author(s)
Asami, T, Ito, T, Fukumitsu, H., Nomoto, H., Furukawa, Y., Furukawa, S
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Journal Title
Biochem Biophys Res Commun 344
Pages: 941-947
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of AMP N_1-oxide in royal jelly as a neurotrophic component for cultured rat pheochromocytoma PC12 cells2006
Author(s)
Hattori, N, Nomoto, H, Mishima, S, Inagaki, S, Goto, M, Sako, M, Furukawa S
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Journal Title
Biosci Biotechnol Biochem 70
Pages: 897-906
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Comparison of FGF1 (aFGF) expression between the dorsal motor nucleus of vagus and the hypoglossal nucleus of rat2006
Author(s)
Toyoda, K, Okano, H, Bamba, H, Hisa, Y, Oomura, Y, Imamura, T, Furukawa, S, Tooyama, I
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Journal Title
Acta Histochem Cytochem 39
Pages: 1-7
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAP kinase.2006
Author(s)
Nishina, A, Kimura, H, Sekiguchi, A, Fukumoto, R, Nakajima, S, Furukawa, S
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Journal Title
J Lipid Res 47
Pages: 1434-1443
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Localization of fibroblast growth factor-1 in cholinergic neurons innervating the rat larynx.2006
Author(s)
Okano, H, Toyoda, K, Bamba, H, Hisa, Y, Oomura, Y, Imamura, T, Furukawa, S, Kimura. H, Tooyama, I
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Journal Title
J Histochem Cytochem 54
Pages: 1061-1071
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Brain-derived neurotrophic factor participates in determination of neuronal laminar fate in the developing mouse cerebral cortex.2006
Author(s)
Fukumitsu, H, Ohtsuka, M, Murai, R, Nakamura, H, Itoh, K, Furukawa, S
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Journal Title
J Neurosci 26 (51)
Pages: 13218-13230
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Protective effect of 4-methylcatechol against cell death of neural stem cells2008
Author(s)
Furukawa, Y, Urano, T, Minamimura, M, Nakajima, M, Kaku, T, Furukawa S
Organizer
The 128th Annual Meeting of The Pharmaceutical Society of Japan
Place of Presentation
Yokohama
Year and Date
2008-03-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Araie M, Hara H. A time-dependent change in the lateral genuculate body of animal model of the NMDA-induced degeneration of the retina2007
Author(s)
Ito, Y, Shimazawa, M, Inokuchi, Y, Fukumitsu, H, Furukawa, S
Organizer
The 50th Annual Meeting of the Japanese Society for Neurochemistry
Place of Presentation
Yokohama
Year and Date
2007-09-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Leu-lle increases GDNF through CREB activation by Hsp90/Akt signaling pathway. The 49th Annual Meeting of the Japanese Society for Neurochemistry2006
Author(s)
Nitta, A, Cen Xiaobo, Ohtani, S, Ozawa, N, Niwa, M, Furukawa, S, Nabeshima, T
Organizer
The 49th Annual Meeting of the Japanese Society for Neurochemistry
Place of Presentation
Nagoya
Year and Date
20060914-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Royal jelly enhances neuronal differentiation of cultured neural stem cells2006
Author(s)
Hattori, N, Araki, Y, Sakamoto, T, Mishima, S, Nomoto, H, Furukawa, S
Organizer
The 49th Annual Meeting of the Japanese Society for Neurochemistry
Place of Presentation
Nagoya
Year and Date
20060914-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Identification of lysophosphatidylethanolamine in grifola frondosa as a molecule with neuroprotective and/or neurotrophic activities toward cultured PC12 cells via activation of MAP kinase.2006
Author(s)
Nishina, A, Kimura, H, Sekiguchi, A, Fukumoto, R, Nakajima, S, Furukawa, S
Organizer
The 79th Annual Meeting of the Japanese Biochemical Society
Place of Presentation
Kyoto
Year and Date
2006-06-21
Description
「研究成果報告書概要(欧文)」より
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