HUMAN BRAIN ANTIOXIDANT LEVELS MEASURED IN VIVO AS A FUNCTION OF AGE AND DIET

体内测量的人脑抗氧化水平与年龄和饮食的关系

• 批准号: 8362817
• 负责人: Melissa J Terpstra
• 金额: $ 1.51万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362817
• 关键词: Age; Age-associated memory impairment; Aging; American; Antioxidants; Appearance; Ascorbic Acid; Biological Assay; Brain; Chemicals; Dependence; Development; Diagnosis; Diet; Early Diagnosis; Early treatment; Elderly; Etiology; Funding; Goals; Grant; Human; Individual; Intervention; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Monitor; NMR Spectroscopy; National Center for Research Resources; Nature; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Oxidative Stress; Plague; Population; Prevalence; Prevention; Principal Investigator; Reduced Glutathione; Research; Research Design; Research Infrastructure; Resources; Serum; Signal Transduction; Source; Supplementation; Symptoms; Therapeutic Intervention; Time; United States National Institutes of Health; Variant; base; cost; in vivo; interest; neurochemistry; normal aging; novel; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite extensive efforts focused on preventing and treating age related cognitive decline, this debilitating condition continues to plague the American population, and is projected to increase dramatically in prevalence unless appropriate interventions are discovered. Due to the irreversible nature of neurodegeneration, prevention, early diagnosis and treatment are imperative. Although oxidative stress is known to be involved early in the etiologies of both normal aging and neurodegenerative disease, lack of a noninvasive assay for brain oxidative status has limited development of antioxidant based interventions. The goal of this proposal is to provide a noninvasive assay for human brain antioxidant concentrations that can be used to: identify influences responsible for compromised antioxidant levels, diagnose reduced antioxidant capacity prior to appearance of symptoms or structural damage, and monitor antioxidant capacity throughout therapeutic intervention. In specific aim 1, a novel noninvasive magnetic resonance spectroscopy (MRS) assay will be used to quantify levels of the two most concentrated chemical antioxidants in the central nervous system, reduced glutathione (GSH) and vitamin C (Asc) in two homogenous human populations. In specific aim 2, this antioxidant profile will be measured under the respective endogenous and exogenous influences of aging and diet. The research design will start with measuring inter- and intra- individual variation of the antioxidant profile under constant experimental conditions. Next, this noninvasive assay will be used to determine whether previous post mortem findings of a 25% decrease in human brain Asc concentration with increasing age will be replicated in vivo. Finally, antioxidant concentrations will be measured in the elder group both before and after administration of vitamin C supplementation. Double edited 1H MRS will be used to measure antioxidant profiles from anatomically matched cortical volumes of interest in vivo. Editing is a specialized form of MRS routinely used to resolve one signal of interest from overlapping signals in vivo. Double editing is a novel application that will be used to resolve two signals, i.e. Asc and GSH resonances in the same amount of time previously required to measure one. Seven additional neurochemical concentrations will be co-measured with but resolved from Asc and GSH, and will be evaluated for dependence upon age and diet, as will serum Asc levels.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 尽管大量努力着重于预防和治疗与年龄相关的认知下降，但 这种衰弱的状况继续困扰着美国人口，预计将增加 除非发现适当的干预措施，否则急剧出现。由于神经退行性的不可逆转性，预防，早期诊断和治疗是必要的。尽管已知氧化应激涉及正常衰老和神经退行性疾病的病因，但缺乏针对脑氧化状态的无创测定的基于抗氧化剂的干预措施的发展有限。该提案的目的是为人脑抗氧化剂浓度提供无创测定，该测定可用于：确定影响造成抗氧化剂水平受损的影响，诊断在出现症状或结构性损害之前降低抗氧化能力，并在整个治疗干预过程中监测抗氧化能力。在特定的目标1中，新型的非侵入性磁共振光谱（MRS）测定法将用于量化中枢神经系统中两种最浓缩的化学抗氧化剂的水平，减少谷胱甘肽（GSH）和维生素C（ASC）在两个同质人群中。在特定的目标2中，这种抗氧化剂的特征将在各自的内源性和外源性影响下的衰老和饮食影响下进行测量。研究设计将始于在恒定的实验条件下测量抗氧化剂特征的间和内部变化。接下来，该无创测定将用于确定先前的验尸后发现，随着年龄的增长，人脑ASC浓度降低25％的结果是否会在体内复制。最后，在补充维生素C的施用之前和之后，将在老年组中测量抗氧化剂浓度。双重编辑的1H MRS将用于测量体内感兴趣的解剖学皮质体积的抗氧化剂谱。编辑是MRS的一种专业形式，通常用于从体内重叠信号来解决一个感兴趣的信号。 双重编辑是一种新颖的应用，该应用将用于解析两个信号，即以相同的测量时间所需的时间和GSH共振。将与ASC和GSH共同测量七个其他神经化学浓度，并将对年龄和饮食的依赖进行评估，以及血清ASC水平也是如此。