Cellular Indicators Of Neuronal Insult

该项目研究了神经元和神经胶质细胞以及神经系统损伤中这些细胞之间的相互作用/信号传导。在神经系统中，小胶质细胞在决定神经元细胞死亡中的调节已成为一个主要的生物学问题。在这个项目中，我们研究了一些事件发生后，损伤的神经系统，包括小胶质细胞激活，星形胶质细胞增生，神经元坏死和损失的反应级联。我们已经证明了在化学诱导的小鼠海马损伤中促炎细胞因子、趋化因子、凋亡因子和细胞周期蛋白的时空响应模式。数据表明，细胞周期调控是至关重要的阶段特异性反应的小胶质细胞在整个模式的神经退行性病变。细胞周期mRNA和TNF受体mRNA的特异性已确定使用激光捕获显微切割和免疫组织化学共定位到不同的神经元群体与不同的细胞命运。未来的研究是基于这样的假设，即神经元和小胶质细胞通过细胞周期调节反应的各个阶段进展，并且细胞衰老可能与显著神经元变性区域中小胶质细胞的巨噬细胞表型有关。

This project examined neuronal and glial cells and interaction/signalling between these cells in nervous system injury. Within the nervous system, regulation of microglia cells in determining neuronal cell death has become a major biological question. In this project we examine a number of events that occur upon injury to the nervous system including the response cascade of microglia activation, astrogliosis, neuronal necrosis and loss. We have demonstrated a spatio-temporal pattern of response for pro-inflammatory cytokines, chemokines, apoptotic factors, and cell-cycle proteins in chemical-induced injury of the mouse hippocampus. Data suggest that cell cycle regulation is critical to the stage specific response of microglia cells in the full pattern of neurodegeneration. The specificity of cell cycle mRNA and TNF receptor mRNA has been determined using laser capture microdissection and immunohistochemical co-localization to distinct neuronal populations with differing cell fates. Future Research is based upon the hypothesis that neurons and microglia progress through various stages of a cell cycle regulatory response and that cell senescence may be related to the macrophage phenotype of the microglia cell in regions of significant neuronal degeneration.