Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease

这个补充是为了支持博士生阿里尔Nieves谁是拉丁美洲女性和美国公民。的 候选人Ariel Nieves将参加以下与目标1相关的研究活动：疗效和 Mg 2+减轻氧化应激和神经炎症的机制及目的2： Mg ~（2+）抑制Aβ诱导的突触丢失和功能障碍。在目标1中，候选人将检查是否以及如何 升高的Mg 2+水平将减少来自线粒体和/或NADPH的活性氧（ROS 寡聚体Aβ42刺激后的氧化酶。然后，我们将研究NFκB通路介导的 如果Mg 2+水平升高，则会抑制促炎酶考克斯-2和iNOS的表达， 以及细胞因子分泌（例如，IL-1、IL-6和TNFα）。最后，为了进一步验证Mg ~（2+）对细胞的保护作用， 氧化应激和炎症抑制，类似的测试将在神经炎性AD中进行 小鼠模型。在目标2中，候选人将研究Mg 2+对Aβ诱导的突触改变的疗效。 结构（例如棘和PSD-95）和功能（例如AMPAR介导的mEPSC），以及对 体外Aβ诱导的tau蛋白过度磷酸化和线粒体片段化。此外，突触可塑性 还将使用LTP/LTD测量来评估Mg 2+处理后AD小鼠中的认知缺陷 Morris水迷宫和新物体识别任务。 已经为候选人制定了一个强有力的培训计划，以便为研究做出智力贡献， 并提高她的研究技能和知识有关的神经科学领域与老龄化， 老年痴呆症的研究阿里尔的研究能力将通过严格的培训和 成为一个有生产力的研究人员后，培训。此外，学员的发展将通过以下方式得到加强： 一个结构化的辅导活动计划，为她提供技能、知识和经验，使她做好准备， 在她的职业道路上出类拔萃。指导计划遵循公认的科学和专业的指导， 关于如何提高受训者经验的标准。

This supplement is to support a PhD student Ariel Nieves who is a Latino female and a citizen of USA. The candidate Ariel Nieves will participate in the following research activities related to Aim 1: Efficacy and mechanism of Mg2+ on reducing oxidative stress and neuroinflammation and Aim 2: Efficacy and mechanism of Mg2+ on inhibiting Aβ-induced synaptic loss and dysfunction. In Aim 1, the candidate will examine if and how elevated Mg2+ level will reduce reactive oxygen species (ROS) originated from mitochondria and/or NADPH oxidase after oligomeric Aβ42 stimulation. Then, we will investigate the involvement of NFκB pathway-mediated inflammation, and if elevated Mg2+ level will inhibit pro-inflammatory enzymes COX-2 and iNOS expression, as well as cytokines secretion (e.g., IL-1, IL-6, and TNFα). Last, to further validate the protective role of Mg2+ in oxidative stress and inflammation suppression, similar testing will be carried out in neuro-inflammatory AD mouse models. In Aim 2, the candidate will study the efficacy of Mg2+ on Aβ-induced alterations in synaptic structures (e.g. spine and PSD-95) and function (e.g. AMPAR-mediated mEPSCs), as well as on inhibition of Aβ-induced tau hyperphosphorylation and mitochondrial fragmentation in vitro. In addition, synaptic plasticity and cognitive deficits in AD mouse after Mg2+ treatment will be evaluated using LTP/LTD measurements as well as Morris water maze and novel-object recognition task, respectively. A robust training plan has been put in place for the candidate to contribute intellectually to the research, and to enhance her research skills and knowledge regarding the field of neuroscience related to aging and Alzheimer’s research. Ariel’s research capability will be substantially enhanced through a rigorous training and become a productive researcher after the training. Moreover, the trainee’s development will be enhanced through a program of structured mentoring activities to provide the skills, knowledge and experience to prepare her to excel in her career paths. The mentoring plan follows the guidance of recognized scientific and professional standards on how to enhance trainee’s experience.