Cellular Indicators Of Neuronal Insult

该项目研究了神经细胞和神经胶质细胞以及这些细胞之间在神经系统损伤中的相互作用/信号传递。在神经系统内，小胶质细胞在决定神经细胞死亡方面的调节已成为一个主要的生物学问题。在这个项目中，我们研究了神经系统损伤时发生的一些事件，包括小胶质细胞激活、星形胶质细胞增生、神经元坏死和丢失的反应级联反应。我们已经证明了在化学诱导的小鼠海马区损伤中，促炎症细胞因子、趋化因子、凋亡因子和细胞周期蛋白的反应具有时空模式。数据表明，细胞周期调节对小胶质细胞在整个神经退行性变模式中的阶段特异性反应至关重要。用激光捕获显微切割和免疫组织化学共定位技术，对不同细胞命运的不同神经元群体，确定了细胞周期mRNA和肿瘤坏死因子受体mRNA的特异性。未来的研究是基于这样的假设，即神经元和小胶质细胞在细胞周期调节反应的不同阶段进行，细胞衰老可能与显著神经元变性区域的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.