Project/Area Number |
10470001
|
Research Category |
Grant-in-Aid for Scientific Research (B).
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General anatomy (including Histology/Embryology)
|
Research Institution | ASAHIKAWA MEDICAL COLLEGE |
Principal Investigator |
KIYAMA Hiroshi Asahikawa Medical College, Faculty of Medicine, Professor, 医学部, 教授 (00192021)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥7,800,000 (Direct Cost: ¥7,800,000)
|
Keywords | Neuronal cell death / Regeneration / Neurite elongation / Hypoglossal nerve / Nerve injury / Adenovirus / Gene transfer / 遺伝子導入 / TC10 / GDNF / 軸策伸展 / アデノウィルス / 神経細胞死 / Cre-LoxP / 細胞死防御 / 運動ニューロン |
Research Abstract |
In an attempt to explore the molecular basis of nerve regeneration process, we have employed differential display-PCR to identify genes whose mRNA expression were up-regulated in injured hypoglossal motor neurons, and succeeded in isolating both novel as well as known molecules with possible association with neuronal survival and regeneration. To rescue or repair injured neurons, the adenovirus mediated gene transfer is one of intriguing means. We thus attempted to establish adenovirus mediated gene transfer system using rat. After establishing the gene transfer system specific to injured motor neurons, we have revealed distinct functional differences between two signaling pathways (P13K-mediated and ERK-mediated pathways downstream growth factor receptors) using our adenovirus system. In addition, we have also revealed a novel activity of Akt on neurite elongation both in vitro and in vivo. Functional significance of other molecules are also revealed by using this adenovirus mediated gene transfer system. For instance a novel Rho family protein TC10 was proved to have a function on neurite elongation. The results obtained in the present project provide useful tool for the nerve regeneration studies, in which the function of a certain molecule are examined in experimental animal, and also open up a possibility of therapeutic intervention in clinical conditions like brain trauma, ischaemia, or neurodegenerative conditions like ALS, Parkinson's disease, etc.
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