Targetted transfection of adenovirus vector carrying brain-derived neurotrophic factoe gene prevents loss of mouse anterior horn neurons in vivo sustaining mechanical compression.
| Project/Area Number |
15591571
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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 |
Orthopaedic surgery
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| Research Institution | UNIVERSITY OF FUKUI (2004)
福井医科大学 (2003) |
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Principal Investigator |
UCHIDA Kenzo University of Fukui Hospital, Lecturer, 医学部附属病院, 講師 (60273009)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Hisatoshi UNIVERSITY OF FUKUI, FACULTY OF MEDICINE, Professor, 医学部, 教授 (00165060)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | spinal cord ingury / neurotrophic factor / gene transfection / 遺伝子治療 |
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| Research Abstract |
Study Design. Immunohistochemical analysis of the expression and localization of brain-derived neurotrophic factor (BDNF), chorine acetyltransferase (ChAT), and activity of acetylcholine esterase (AChE) after adenovirus (Adv)-mediated BDNF gene transfer in and around the area of mechanical compression in the cervical spinal cord of the hyperostotic mouse (twy/twy).
Objective. To investigate the neuroprotective effect of targeted AdV-BDNF gene transfection in the twy mouse with spontaneous chronic compression of the spinal cord anterior horn neurons.
Summary of Background Data. Several studies reported the neuroprotective effects of neurotrophins on injured spinal cord motoneurons. However, no report has described the effect of targeted retrograde neurotrophic gene delivery on motoneuron survival in vivo in chronic compression lesions of the cervical spinal cord resembling lesions of myelopathy.
Methods. LacZ marker gene using adenoviral vector (AdV-LacZ) was used to evaluate retrograde de
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livery from the stemomastoid muscle to the cervical spinal cord anterior horn neurons in adult twy mice (16-week-old) and Institute of Cancer Research (ICR) mice (control). Four weeks after the AdV-LacZ or AdV-BDNF injection, the compressed cervical spinal cord was removed en bloc for immunohistological investigation of □-galactosidase activity and immunoreactivity and immunoblot analyses of BDNF. The number of anterior horn neurons was counted using Nissl, ChAT and ACNE staining.
Results. Spinal accessory motoneurons between C1 and C3 segments were successfully transfected by AdV-LacZ in both twy and ICR mice after targeted intramuscular injection. Immunoreactivity to BDNF was significantly stronger in AdV-BDNF-gene transfected twy mice than in AdV-LacZ-gene transfected mice. At the cord level showing the maximum compression in Adv-BDNF-transfected twy mice, the number of anterior horn neurons was significantly higher in the topographic neuronal cell counting of Nissl-, ChAT-and AChE-stained samples, than in Adv-LacZ-injected twy mice.
Condusion. Targeted AdV-BDNF-gene delivery via the sternomastoid muscle significantly increased Nissl-stained anterior horn neurons, which lacked nuclear chromatolysis and showed neurite arborization, and enhanced ChAT and ACNE immunoreactivities in the twy mouse anterior horn neurons. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal survival even under chronic mechanical compression. Less
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Metabolic neuroimaging of the cervical spinal cord in patients with compressive myelopathy : a high-resolution positron emission tomography study.2004
Author(s)
Uchida, K., Kobayashi, S., Yayama, T., Kokubo, Y., Nakajima, H., Kakuyama, M., Sadato, N., Tsuchida, T., Yonekura, Y., Baba, H.
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Journal Title
J Neurosurg (Spine 1) 101(1)
Pages: 72-79
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Uchida, K., Baba, H., Furukawa, S., Omiya, M., Kokubo, Y., Kubota, C., Nakajima.: "Increased expression of neurotrophins and their receptors in the mechanically compressed spinal cord of the spinal hyperostotic mouse(twy/twy)"Acta neuropathologica. 106. 29-36 (2003)
