ZN DEFICIENCY IMPAIRS BBB INTEGRITY FR OXIDATIVE STRESS

描述：(逐字摘自申请者的摘要)锌在 脑功能和神经生物学得到了广泛的认可，许多人类 神经系统疾病被认为与缺锌有关。然而，这种机制 饮食中的锌缺乏可能导致大脑--一个器官--的病理 对氧化损伤高度敏感，目前尚不清楚。对……的调查 氧化应激对大脑功能的影响通常会因 脑组织产生氧化伪影指数的高倾向 体内应激。我们将率先应用非侵入性活体磁共振和 用~(31)P-核磁共振技术研究锌营养在维持玉米生长发育中的作用 大鼠血脑屏障完整性与脑能量代谢 氧化应激。此外，我们将确定可能的细胞和分子 氧化应激下锌缺乏症的病理机制。因此人们关注的焦点 这项建议的目的是研究锌营养在应对 氧化应激可预防脑部疾病。这样做的长期目标是 研究是为了了解这种关系背后的基本机制 膳食锌与最佳中枢神经系统(CNS)功能之间的关系。我们 推测次优的锌营养会削弱血脑屏障的完整性 叠加锌缺乏的氧化应激扰乱保护性 血脑屏障的功能，这一事件可能在许多 大脑紊乱。因此，大脑动态平衡的紊乱 血脑屏障完整性的丧失可能会导致能量代谢受损和增加 大脑内的氧化应激，一系列代谢和生化反应 锌缺乏对脑发育影响的变化 精神错乱。因此，这个项目的假设是锌保护血脑屏障 通过抗氧化和膜稳定来对抗氧化应激 因此有助于维持大脑代谢的动态平衡 并预防脑部疾病。为了检验这一假设，我们将量化变化 在血脑屏障通透性和大脑能量代谢方面，评估 自由基防御和自由基生成，并测量 染锌对缺锌大鼠脑组织氧化损伤的影响 高氧症。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对 锌在脑部疾病病因学中的作用机制 制定更好的疾病预防战略。

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.