NMDA RECEPTORS AND DA IN A MODEL OF OXIDATIVE INJURY

Maragos博士是一位敬业的医生/科学家， 成为一名学术神经学家他的科学目标是 了解导致神经细胞死亡的因素。的 候选人最近加入了神经病学系在大学 肯塔基州作为一个终身助理教授。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 将把80%的时间用于实验室相关活动。他的担保人， 唐·加什博士他是基底神经节研究领域的领导者， 将监督他的调查强大的神经科学社区在 大学将为Maragos博士提供必要的知识 互动和合作的潜力。除了研究， 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。 在获奖的晚年，他将参与分子生物学 在冷泉港的研讨会上， 来学习他计划融入未来研究的技术。5%的 时间将致力于教学居民，研究生和 承担有限的行政责任。的首要目标 该建议是开发一种新的体内方法， 活性氧（ROS）脑损伤，并使用该模型 探讨活性氧对大鼠纹状体的毒性作用机制。马拉格斯医生 将在脑内注射抗氧化酶的抑制剂， 组织损伤他将使用几种方法评估细胞毒性反应。 组织化学方法，他有经验， 免疫组织化学和神经化学方法学（即，HPLC ROS生产的确定），他将在颁奖期间学习 期他使用了几种方法来改变突触多巴胺的化学性质， 将使用这个模型来研究多巴胺或其代谢物 增强ROS毒性。他将研究活性氧对NMDA的相互作用 受体功能，通过测定NMDA拮抗剂对ROS- 诱导的组织损伤以及ROS是否通过 测量体内[3 H] MK-801与开放通道的结合。预计 拟议的研究将提供有价值的数据， 神经递质参与ROS毒性，并允许发展 机械疗法

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.