COBRE: UNM: MECHANISMS OF DELAYED CELL DEATH

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。谷氨酸受体过度激活引起的细胞损伤过程被称为兴奋性毒性，可能涉及一系列疾病，包括缺血、癫痫发作、帕金森病、S病和肌萎缩侧索硬化。维持适当代谢功能的策略可能是设计未来兴奋性毒性损伤治疗干预措施的关键考虑因素。此类干预的成功依赖于对不同类型谷氨酸兴奋性的代谢需求的了解。这一子项目评估了急性海马片的线粒体功能，以评估谷氨酸受体刺激后线粒体功能原位变化的机制。主要的重点是评估多种成像方法。内源性代谢信号(NADH和黄素蛋白)的荧光成像是一种已经在许多生化和一些成像研究中得到验证的方法，但由于高分辨率成像应用于完整的制剂，该方法重新引起了人们的兴趣。单光子和多光子成像将用于识别线粒体信号的细胞来源，并研究突触刺激和外源性谷氨酸受体激动剂产生信号的机制。这项工作的总体目标是开发能够在兴奋性毒性损伤的进展过程中对复杂脑组织中的线粒体功能进行高分辨率监测的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The process of cell damage following excessive glutamate receptor activation has been termed "excitotoxicity", and may be involved in a range of disorders including ischemia, seizure activity, Parkinson?s Disease and ALS. Strategies that maintain appropriate metabolic function may be a critical consideration for the design of future therapeutic interventions for excitotoxic injuries. The success of such interventions relies on understanding metabolic demands involved in different types of glutamate excitoxicity. This subproject evaluates mitochondrial function in acute hippocampal slices, to evaluate the mechanisms involved in mitochondrial function changes in situ, following glutamate receptor stimulation. The major emphasis is to evaluate multiple imaging approaches. Fluorescence imaging of intrinsic metabolic signals (NADH and flavoprotein) is an approach which has been validated in many previous biochemical and some imaging studies, but which has received a resurgence of interest because of the application of high resolution imaging to intact preparations. Single- and multi-photon imaging will be used to identify cellular sources of mitochondrial signals, and to study mechanisms underlying signals generated by synaptic stimulation, and by exogenous application of glutamate receptor agonists. The overall goal of this work is to develop approaches that can provide high resolution monitoring of mitochondrial function in complex brain tissue, during the progression of excitotoxic injury.