COBRE: UNM: MECHANISMS OF DELAYED CELL DEATH

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。谷氨酸受体过度激活后的细胞损伤过程被称为“兴奋性毒性”，可能与一系列疾病有关，包括缺血、癫痫发作、帕金森病等。s疾病和渐冻症。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。这种干预的成功依赖于对不同类型谷氨酸兴奋性所涉及的代谢需求的理解。本子项目评估急性海马切片的线粒体功能，以评估谷氨酸受体刺激后线粒体功能原位改变的机制。主要的重点是评估多种成像方法。固有代谢信号（NADH和黄素蛋白）的荧光成像是一种已经在许多先前的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在完整制剂中的应用，它又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，并研究突触刺激和谷氨酸受体激动剂外源性应用产生的信号机制。这项工作的总体目标是开发一种方法，可以在兴奋性毒性损伤的进展过程中提供复杂脑组织中线粒体功能的高分辨率监测。

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.