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Prevention of injured neuron death by adennovirus vector.

腺病毒载体预防受损神经元死亡。

基本信息

批准号：
10470001
负责人：
KIYAMA Hiroshi
金额：
$ 9.6万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470001/
关键词：
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

项目摘要

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.

为了探索神经再生过程的分子基础，我们采用差异显示-PCR技术鉴定了损伤的舌下神经运动神经元中mRNA表达上调的基因，并成功地分离了可能与神经元存活和再生相关的新分子和已知分子。腺病毒介导的基因转移是拯救或修复受损神经元的一种有趣的手段。因此，我们尝试建立腺病毒介导的大鼠基因转移系统。在建立了针对受损运动神经元的基因转移系统后，我们使用我们的腺病毒系统揭示了两种信号传导途径（P13 K介导的和ERK介导的下游生长因子受体途径）之间的明显功能差异。此外，我们还发现了一种新的活性Akt神经突起的伸长在体外和体内。利用这种腺病毒介导的基因转移系统还揭示了其他分子的功能意义。例如，一种新的Rho家族蛋白TC 10被证明具有神经突起延伸的功能。本项目中获得的结果为神经再生研究提供了有用的工具，其中在实验动物中检查了某些分子的功能，并且还开辟了在临床条件下治疗干预的可能性，如脑创伤，缺血，或神经退行性疾病，如ALS，帕金森病等。