The roles of cytokines and neurotrophins in the regenerative process of nervous system

细胞因子和神经营养因子在神经系统再生过程中的作用

基本信息

批准号：
09480215
负责人：
SENBA Emiko
金额：
$ 6.21万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

The involvement of cytokines and neurotrophic/neuroprotective factors in the process of injury/regeneration were investigated in various regions of the nervous system. Three types of injury models were prepared in rats ; (1)chronic constriction injury (CCI) or axotomy of the sciatic nerve, (2) crush injury of the spinal cord and (3) focal cerebral ischemia/reperfusion model. The spacial and temporal expression patterns of proteins and mRNAs of IEGs, cytokines and neurotrophins were investigated and cell types expressing thse molecules were determined. Expression of receptor components of IL-6 family cytokines, such as gp130, LIFRβ, IL-6R, OSMR, and signal transduction molecules of JAK-STAT pathway were investigated in the brain of rats and mice, in order to explore the roles of cytokines of this family in the nervous system. We found that these receptor components were expressed in cerebellar Purkinje cells. Overexpression of LIF in mice induced marked dendritic atrophy of Purkinje cel … More ls. Reorganization of dendro-dendritic synapses in the ex vivo model of superior cervical ganglion was inhibited by addition of serum in the medium, indicating that serum-derived factors are involved in the regulation of dendritic morphology of neurons. Experiments in the peripheral tissues, such as muscles, cornea and stomach, indicated that cytokines play important roles in the regeneration process, which is triggered by IEGs expression after injury. Migration of corneal epithelial cells was not initiated in c-fos knockout mice and in cultured cornea treated with antisense ODNs for c-fos and c-jun mRNAs. We showed that AP-1 is also involved in the regulation of BDNF and NT-3 gene expression using vascular smooth muscle cells. AP-1 was shown to negatively control the expression of NT-3 gene. E1A-and E1B-deleted adenovirus (AdV) containing EGFP reported gene insert under the control of CAG promoter was constructed and used in the in vivo experiment. Injection of this AdV-EGFP into the sciatic nerve or in the skin resulted in labeling of DRG neurons. Less

在神经系统的各个区域，研究了细胞因子和神经营养/神经保护因子在损伤/再生过程中的参与。在大鼠中准备了三种类型的损伤模型。（1）坐骨神经的慢性收缩损伤（CCI）或轴切开术，（2）脊髓的挤压损伤和（3）局灶性脑缺血/再灌注模型。研究了IEG，细胞因子和神经营养蛋白的蛋白质和mRNA的空间和临时表达模式，并确定表达ThSE分子的细胞类型。在大鼠和小鼠的大脑中研究了IL-6家族细胞因子的受体成分，例如GP130，LIFRβ，IL-6R，OSMR和JAK-STAT途径的信号转导分子的表达，以探索该家族的细胞因子在神经系统中的作用。我们发现这些受体成分在小脑Purkinje细胞中表达。小鼠中LIF的过表达诱导了Purkinje Cel的明显树突状萎缩…更多。通过在培养基中添加血清，抑制了超宫颈神经节的离体模型中的Dendro Dendritic突触的重组，这表明血清衍生的因子与神经元的树突状形态有关。外周组织中的实验，例如肌肉，角膜和摊位，表明细胞因子在再生过程中起重要作用，这是由IEG损伤后的IEG表达触发的。角膜上皮细胞的迁移并未在C-FOS敲除小鼠和用反义ODN治疗的C-FOS和C-JUN mRNA的培养的角膜中启动。我们表明，使用血管平滑肌细胞对BDNF和NT-3基因表达的调节也参与了AP-1。 AP-1被证明对NT-3基因的表达进行负面控制。在CAG启动子的控制下，含有EGFP的E1A和E1B污染腺病毒（ADV）在体内实验中构建并使用。将此Adv-EGFP注入坐骨神经或皮肤中，导致DRG神经元的标记。较少的