权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Functional significance of tumor necrosis factor alpha in inducing retinal ganglion cell death by using gene targeting method

肿瘤坏死因子α基因靶向诱导视网膜神经节细胞死亡的功能意义

基本信息

批准号：
11671758
负责人：
SHIODA Seiji
金额：
$ 2.5万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671758/
关键词：
TNFα Delayed neuronal cell death Signal transduction Transgenic mouse 虚血 Tumor Necrosis Factor-α KO mouse Retina Ischemia PACAP Neurotrophic Factor

项目摘要

We have first demonstrated that the ischemia-induced apoptosis of neurons in the ganglion cell layer of the mouse retina with cardiac arrest model. The mice were cardiac arrested for 5 min and reperfused after the ischemia. We found that the ganglion cells were degenerating with shrinkage of cells, nuclear condensations, DNA fragmentations but no disruptions of mitochondria, suggesting apoptotic changes in these cells. Tumor necrosis factor alpha (TNFα) is shown to induce neuronal cell death in the hippocampus and neocortex in brain and it is supposed to be involve in neuronal cell death in retina. Therefore, we used TNFα-deficient mice to demonstrate whether it induces a delayed neuronal cell death (apoptosis) in mice retina. Many apoptotic neuronal cell death in the ganglion cell layer was significantly observed in the wild-type ones as compared with TNFα-deficient ones. The caspase-3 activity in the ThF*-deficient ones was less than that of the wild-type ones. These results suggest that TNFa acts to stimulate the caspase-3 pathway, thereby inducing retinal ganglion cell death.

我们首次用心跳骤停模型证明了缺血诱导小鼠视网膜神经节细胞层神经元的凋亡。小鼠心脏停搏5min，缺血后再灌流。我们发现神经节细胞变性，细胞皱缩，核固缩，DNA片段化，但没有线粒体的破坏，提示这些细胞发生了凋亡的变化。肿瘤坏死因子α可诱导大鼠海马区和大脑皮层神经细胞死亡，可能与视网膜神经细胞死亡有关。因此，我们使用肿瘤坏死因子α缺陷小鼠来证明它是否诱导小鼠视网膜迟发性神经细胞死亡(细胞凋亡)。野生型与肿瘤坏死因子α缺陷型相比，神经节细胞层有大量的神经细胞死亡。THF*缺陷株的caspase-3活性低于野生型。这些结果表明，TNFa可以刺激caspase-3途径，从而诱导视网膜神经节细胞死亡。

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Imaizumi H, Miznshima H, Matsumoto H, Dohi K, Matsumoto K, Horai R, Asano M, Iwakura Y, Funahashi H, Shioda S: "Increased expression of interleukin-lp in mouse hippocampus after global ischemia."Acta Histochem Cytochem. 343. 357-362 (2001)

Imaizumi H、Miznshima H、Matsumoto H、Dohi K、Matsumoto K、Horai R、Asano M、Iwakura Y、Funahashi H、Shioda S：“整体缺血后小鼠海马中白细胞介素-lp 的表达增加。”Acta Histochem Cytochem。