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

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神经系统的各个区域进行了研究。在大鼠中制备三种类型的损伤模型：（1）坐骨神经的慢性压迫性损伤（CCI）或轴性切断，（2）脊髓的挤压性损伤和（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因子的蛋白质和mRNA的时空表达模式，并确定了表达这些分子的细胞类型。本研究通过观察IL-6家族细胞因子的受体成分gp 130、LIFRβ、IL-6 R、OSMR以及JAK-STAT信号转导通路中的信号转导分子在大、小鼠脑内的表达，探讨该家族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浦肯野细胞中表达。LIF过表达诱导小鼠浦肯野细胞树突状萎缩 关于我们 LS.在离体模型的上级颈神经节的树突-树突突触的重组被抑制血清中加入的培养基，表明血清衍生因子参与调节树突状神经元的形态。在外周组织如肌肉、角膜和胃中的实验表明，细胞因子在损伤后由IEGs表达触发的再生过程中起重要作用。在c-fos基因敲除小鼠和用c-fos和c-jun mRNA反义寡核苷酸处理的培养角膜中，角膜上皮细胞的迁移没有开始。我们发现AP-1也参与了血管平滑肌细胞BDNF和NT-3基因表达的调节。AP-1负调控NT-3基因的表达。构建了含CAG启动子调控下的EGFP报告基因插入片段的E1 A和E1 B缺失腺病毒（AdV），并进行了体内实验。将该AdV-EGFP注射到坐骨神经或皮肤中导致DRG神经元的标记。少

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