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

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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.