The Effects of Microglia on Oligodendrocyte Cell Death

描述（由申请人提供）： 少突胶质细胞（oligo）细胞死亡响应于若干病理生理过程而发生，包括缺血、缺氧、感染和创伤。几个实验室已经表明，在上述损伤模型中，寡核苷酸会因过量的神经递质谷氨酸而死亡或受损。然而，关于寡核苷酸对谷氨酸的敏感性有不同的报道，目前还不知道是什么因素导致了这些不同的结果。拟议的研究将开始，以确定受损的中枢神经系统（CNS）的细胞外环境如何改变寡核苷酸对谷氨酸的反应。该提案将重点关注两个因素-氧气变化和小胶质细胞的存在-如何影响寡核苷酸对CNS创伤和疾病期间释放的有毒物质的脆弱性。使用少突胶质细胞和小胶质细胞培养物，无论是在隔离和组合，沿着与氧调节培养箱和谷氨酸受体激动剂红藻氨酸，拟议的实验将有助于确定什么条件和细胞反应在中枢神经系统介导寡核苷酸死亡，并提供洞察未来的治疗，以保护寡核苷酸在多种疾病。

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.