ZN DEFICIENCY IMPAIRS BBB INTEGRITY FR OXIDATIVE STRESS

缺锌会损害血脑屏障完整性和氧化应激

• 批准号: 6531088
• 负责人: TAMMY M BRAY
• 金额: $ 2.05万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6531088
• 关键词: blood brain barrier; brain metabolism; diet therapy; dietary trace element; disease /disorder prevention /control; free radicals; hyperoxia; laboratory rat; magnetic resonance imaging; membrane permeability; nervous system disorder; nuclear magnetic resonance spectroscopy; nutrition disorders; nutrition related tag; oxidative stress; zinc

DESCRIPTION: (Verbatim from the Applicant's Abstract) The importance of Zn in brain function and neurobiology is widely acknowledged, and many human neurological diseases have been linked to Zn deficiency. However, the mechanism by which dietary Zn deficiency may lead to pathology in the brain, an organ highly susceptible to oxidative damage, is not yet clear. Investigations into the effect of oxidative stress on brain function are often complicated by the high propensity of brain tissue to develop artifactual indices of oxidative stress in vivo. We will pioneer the application of non-invasive in vivo MRI and 31P-NMR techniques to study the role of Zn nutrition in maintaining the integrity of the blood brain barrier(BBB) and brain energy metabolism under oxidative stress. Further, we will identify possible cellular and molecular mechanisms for Zn deficiency pathology under oxidative stress. Hence the focus of this proposal is to examine the role of Zn nutrition in coping with oxidative stress to prevent brain disorders. The long term goal of this research is to understand the basic mechanism underlying the relationship between dietary Zn and optimal central nervous system(CNS) function. We speculate that sub-optimal Zn nutrition weakens BBB integrity and that oxidative stress superimposed upon Zn deficiency disrupts the protective function of the BBB, an event that may be pivotal in the pathogenesis of many brain disorders. Consequently, perturbations of cerebral homeostasis following loss of BBB integrity may lead to impaired energy metabolism and increased oxidative stress within the brain, a sequence of metabolic and biochemical changes by which Zn deficiency may contribute to the development of brain disorders. Thus, the hypothesis of this project is that Zn protects the BBB against oxidative stress through its antioxidant and membrane stabilization properties and therefore helps to maintain the homeostasis of brain metabolism and prevent brain disorders. To test this hypothesis, we will quantify changes in BBB permeability and brain energy metabolism, assess the balance between free radical defense and free radical generation, and measure the extent of oxidative damage in the brain of Zn deficient rats during exposure to hyperoxia. In addition, the possible underlying mechanisms will be explored. This research will contribute significantly to our understanding of the mechanistic roles of Zn in the etiology of brain disorders and lead to the development of better strategies for disease prevention.

描述：（逐字摘自申请人摘要）锌在 脑功能和神经生物学是广泛公认的，许多人类 神经系统疾病与锌缺乏有关。然而，机制 饮食中锌缺乏可能导致大脑的病理学， 对氧化损伤高度敏感，目前尚不清楚。调查 氧化应激对脑功能的影响通常因 脑组织更容易产生人为的氧化指数 体内应力。我们将开创非侵入性体内MRI的应用， 利用~（31）P-NMR技术研究锌营养在维持机体免疫功能中的作用 血脑屏障（BBB）和脑能量代谢的完整性 氧化应激此外，我们将确定可能的细胞和分子 氧化应激下锌缺乏病理学的机制。因此， 这项建议的目的是研究锌营养在应对 氧化应激，以防止大脑紊乱。长期目标是 研究的目的是了解这种关系的基本机制， 饮食锌和最佳中枢神经系统（CNS）功能之间的关系。我们 推测次优锌营养削弱BBB完整性， 氧化应激叠加锌缺乏破坏了保护性 BBB的功能，这可能是许多疾病发病机制中的关键事件。 脑部疾病。因此，脑内稳态的扰动， BBB完整性的丧失可能导致能量代谢受损， 大脑中的氧化应激，一系列代谢和生化反应， 锌缺乏可能导致大脑发育的变化 紊乱因此，本项目的假设是锌保护血脑屏障 通过其抗氧化剂和膜稳定性对抗氧化应激 因此有助于维持大脑代谢的稳态 防止大脑紊乱为了验证这一假设，我们将量化 在BBB通透性和脑能量代谢方面， 自由基防御和自由基的产生，并衡量程度， 锌缺乏对大鼠脑组织氧化损伤的影响 高氧。此外，还将探讨可能的潜在机制。 这项研究将大大有助于我们了解 锌在脑疾病病因学中的机械作用，并导致 制定更好的疾病预防战略。