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Isolation and functional analysis of genes related to delayed neuronal death in mouse hippocampus

小鼠海马神经元迟发性死亡相关基因的分离及功能分析

基本信息

批准号：
13470323
负责人：
USHIJIMA Kazuo
金额：
$ 8.96万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470323/
关键词：
ischemic neuronal death gene trapping neuroprotective agents neuronal stem cells glutamate dantrolene propofol ulinastatin 遅発性神経細胞死

项目摘要

We have isolated some unknown genes expressed in the mouse hippocampal CA1 region using a gene trapping method. The function of these genes has been analyzed in the mouse transient cerebral ischemic model, i.e., ligation of bilateral common carotid arteries. Moreover, the gene products are going to be induced into the brain with the use of protein transduction method to determine the functions in ischemia. In the future, more unknown genes related to neuronal injury and protection will be isolated. With regard to treatment of post-ischemic brain injury, we investigated the drugs already used in clinical practice. Then we reported that dantrolene and propofol could reduce the post-ischemic delayed neuronal death in the hippocampal CA1 sub field, and that the neuroprotection is caused by not only the decrease of extracellular glutamate but also antioxidative effects. Furthermore, massive intracerebroventricular ulinastatin, a human urine-derived trypsin inhibitor, could reduce the infarct volume in the rat focal ischemic model of middle cerebral artery occlusion. We are going to study the neuro-protective effects of various agents such as free radical scavengers and anesthetics. Great attention has been paid to the action of neural stem cells, ependymal cells in the subventricular zone, in ischemic brain damage. We demonstarted that ependymal cells migrate, proliferate, and differentiate in response to focal cerebral ischemia in rat model of middle cerebral artery occlusion. In relation to this interesting phenomenon, we are investigating the participation of genes.

我们用基因捕获法分离了小鼠海马CA1区表达的一些未知基因。这些基因的功能已经在小鼠短暂性脑缺血模型中进行了分析，即，结扎双侧颈总动脉。并利用蛋白质转导的方法将基因产物导入脑内，以确定其在缺血状态下的功能。未来，更多与神经元损伤和保护相关的未知基因将被分离出来。关于缺血后脑损伤的治疗，我们调查了临床实践中已经使用的药物。随后我们报道了丹曲林和丙泊酚可减轻缺血后海马CA1区迟发性神经元死亡，其神经保护作用不仅与细胞外谷氨酸的减少有关，还与抗氧化作用有关。此外，大量侧脑室注射尿胰蛋白酶抑制剂乌司他丁可减少大鼠大脑中动脉闭塞局灶性脑缺血模型的梗死体积。我们将研究各种药物如自由基清除剂和麻醉剂的神经保护作用。室管膜下区神经干细胞在缺血性脑损伤中的作用已引起广泛关注。我们证明，室管膜细胞迁移，增殖，并在局灶性脑缺血大鼠模型大脑中动脉闭塞的分化。关于这个有趣的现象，我们正在研究基因的参与。