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

在各种神经系统中，细胞因子和神经保护因子在jry/j的过程中的涉及三种类型的损伤模型研究了IEG，细胞因子和神经营养蛋白的RNA的时间表达模式，并确定表达ThSE分子的细胞类型。为了探索该家族的细胞因子在神经系统中，jak-statat的转导途径瓦特的大脑中有瓦特在培养基中血清抑制上囊神经节的离体模型中的突触，表明血清衍生的因素与树突状形态神经元的调节有关细胞因子在再生过程中起着重要的作用，在损伤后IEG表达和用反义ODN治疗的C-Fos C-Jun mRNA的培养的角膜。 NT-3的基因表达使用NT-3基因的SSION。导致DRG神经元的标记