NMDA RECEPTORS AND DA IN A MODEL OF OXIDATIVE INJURY

马拉戈斯博士是一位敬业的医生/科学家，他坚定地致力于 成为一名学术神经学家。他的科学目标是 了解那些导致神经细胞死亡的因素。这个 应聘者最近进入密歇根大学神经病学系 肯塔基州担任终身教职助理教授。美国商务部 神经科为他提供了一个实验室和购买资源 设备和租用技术支持。在整个颁奖期间，他 会把80%的时间花在实验室相关的活动上。他的赞助商， 唐·加什是基底节研究领域的领先者， 将监督他的调查。强大的神经科学界在 大学将为马拉戈斯博士提供必要的智力 互动和协作潜力。除了研究之外， 候选人将花费15%的时间从事临床活动， 主要是在运动和相关的神经退行性疾病领域。 在获奖的最后几年，他将参与分子生物学 在冷泉港举办研讨会，并与大学的科学家合作 学习他计划纳入未来研究的技术。他的5% 时间将专门用于教授住院医生、研究生和 履行有限的行政责任。的主要目标是 这项提议是为了开发一种新的体内方法，用来创造性地 活性氧簇(ROS)对脑损伤的影响，并利用该模型 探讨ROS对啮齿动物纹状体的毒性机制。马拉戈斯医生 将抗氧化酶的抑制剂注射到大脑内以诱导 组织损伤。他将使用几种方法来评估细胞毒性反应 他有经验的组织化学方法和 免疫组织化学和神经化学方法(即高效液相色谱法 ROS产量的确定)，他将在颁奖期间学习 句号。使用几种方法来修饰突触的多巴胺化学，他 将使用这个模型来研究多巴胺或其代谢物 增强ROS毒性。他将研究ROS对NMDA的相互影响 通过测定NMDA拮抗剂对ROS的影响来实现受体的功能 ROS是否通过以下途径促进NMDA受体的激活 体内测定[~3H]MK-801与开放通道的结合。这是意料之中的 拟议的研究将提供关于以下方面的宝贵数据 神经递质参与ROS毒性并允许发生 机械治疗学。

Dr. Maragos is a dedicated physician/scientist who is strongly committed to a career as an academic neurologist. His scientific goal is to understand those factors that contribute to a nerve cell death. The candidate recently joined the Department of Neurology at the University of Kentucky as a tenure-track Assistant Professor. The Department of Neurology has provided him with a laboratory and the resources to purchase equipment and hire technical support. During the entire award period, he will spend 80% of his time on laboratory related activities. His sponsor, Don Gash, P.h.D. who is a leader in the field of basal ganglia research, will oversee his investigations. The strong Neuroscience community at the University will provide Dr. Maragos with essential intellectual interactions and potential for collaboration. In addition to research, the candidate will spend 15% of his time pursuing clinical activities, primarily in the area of movement and related neurodegenerative disorder. In the later years of the award, he will participate in molecular biology workshop at Cold Spring Harbor and work with scientists in the University to learn techniques he plans to incorporate into future studies. 5% of his time will be dedicated to teaching residents, graduate students and fulfilling limited administrative responsibilities. The primary goal of this proposal is to develop a novel in vivo method with which to creative reactive oxygen species (ROS) brain damage and to use this model to investigate the mechanism of ROS toxicity in rodent striatum. Dr. Maragos will inject inhibitors of antioxidant enzymes intracerebrally to induce tissue damage. He will assess the cytotoxic response using several histochemical methods with which he has experience and with immunohistochemical and neurochemical methodology (i.e., HPLC determination of ROS production) that he will learn during the award period. Using several approach to modify synaptic dopamine chemistry, he will use this model to investigate whether dopamine or its metabolite enhance ROS toxicity. He will study the reciprocal effects of ROS on NMDA receptor function by determining the effects on NMDA antagonists on ROS- induced tissue damage and whether ROS enhances NMDA receptor activation by measuring in vivo [3H] MK-801 binding to the open channel. It is expected that the proposed studies will provide valuable data about neurotransmitter involvement in ROS toxicity and allow development of mechanistically based therapeutics.