The Effects of Microglia on Oligodendrocyte Cell Death

描述(由申请人提供)： 少突胶质细胞死亡发生在多种病理生理过程中，包括缺血、缺氧、感染和创伤。几个实验室已经证明，上述损伤模型中的寡核苷酸会因过量的神经递质谷氨酸而死亡或受损。然而，关于寡聚体对谷氨酸的易感性有不同的报道，目前还不知道是什么因素导致了这些不同的结果。拟议中的研究将开始确定受损的中枢神经系统(CNS)中的细胞外环境如何改变寡聚体对谷氨酸的反应。这项提案将重点关注两个因素--氧气的变化和小胶质细胞的存在--如何影响寡聚体对中枢神经系统创伤和疾病期间释放的有毒物质的易感性。利用分离和组合培养的少突胶质细胞和小胶质细胞，以及氧气调节孵化器和谷氨酸受体激动剂红藻氨酸，拟议的实验将有助于确定中枢神经系统中什么条件和细胞反应介导寡聚死亡，并为未来在多种疾病中保护寡聚的治疗方法提供见解。

DESCRIPTION (provided by applicant): Oligodendrocyte (oligo) cell death occurs in response to several pathophysiological processes, including ischemia, hypoxia, infection and trauma. Several laboratories have shown that oligos in the above models of injury die or are damaged by excessive amounts of the neurotransmitter glutamate. However, there are varying reports of just how susceptible oligos are to glutamate, and it is not known what factors are responsible these differing results. The proposed studies will begin to determine how the extracellular environment in a damaged central nervous system (CNS) changes oligos' response to glutamate. This proposal will focus on how two factors - oxygen changes and the presence of microglia - affect oligos vulnerability to toxic substances released during CNS trauma and disease. Using Oligodendrocyte and microglia cultures, both in isolation and combination, along with oxygen-regulating incubators and the glutamate receptor agonist kainic acid, the proposed experiments will help determine what conditions and cellular responses in the CNS mediate oligo death, and provide insights into future therapies to protect oligos in multiple diseases.