Brain aging and antioxidant supplementation

大脑老化和抗氧化剂补充

• 批准号: 7847476
• 负责人: MICHAEL J. FORSTER
• 金额: $ 24.98万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847476
• 关键词: Address; Age; Age-associated memory impairment; Albumins; Animals; Antioxidants; Ascorbic Acid; Auditory; Biological; Biological Markers; Brain; Brain region; Cognitive; Development; Disulfides; Dose; Elderly; Equilibrium; Functional disorder; Glutathione; Goals; Human; Impairment; Intake; Intervention; Learning; Link; Lipids; Maintenance; Malondialdehyde; Memory; Mus; Nature; Neurobiology; Neurodegenerative Disorders; Neurologic; Outcome; Oxidation-Reduction; Oxidative Stress; Plasma; Proteins; Psychomotor Performance; Reaction Time; Regimen; Research Personnel; Sensory; Short-Term Memory; Specific qualifier value; Study Section; Supplementation; Testing; Therapeutic; Time; Treatment Protocols; Treatment outcome; Ubiquinone; Variant; Vitamin E; age related; aging brain; aminothiol; base; behavior test; classical conditioning; cognitive function; functional loss; improved; loss of function; muscle strength; oxidative damage; prevent; research study; response; somatosensory; treatment effect

DESCRIPTION (provided by applicant): The endogenous antioxidants vitamin E, vitamin C, and coenzyme Q (CoQ) are thought to have significant interactions in the maintenance of cellular redox state and in cellular protection form oxidative insult. The proposed project will determine the extent to which these compounds can interact to ameliorate or prevent functional brain aging in mice, when supplemented in two- and three-way combinations. In one experiment (Aim1), supplementation with the antioxidant combinations will be initiated in late life, at age when brain dysfunction is already present. A battery of behavioral tests will be used to estimate the ability of the antioxidant supplementation regimens to reverse age-related losses of cognitive functions (associative learning, working memory, and spatial learning) as well as losses of sensory and psychomotor functions (auditory and somatosensory responsiveness, reaction time, coordination, balance, muscle strength). The same battery of behavioral tests will be used to determine whether or not the antioxidant supplementation regimens can prevent functional losses if supplementation is initiated prior to development of age-related brain dysfunction (Aim2). To determine whether or not beneficial effects of the antioxidative regimens depend on their ability to reduce oxidative stress/damage (Aim 3), brains from the mice tested in the first two aims will be dissected into different regions for determining: (i) amounts of oxidative damage to proteins or lipids (protein carbonyls, thiobarbituric reactive substances), (ii) shifts in glutathione redox state and amounts of aminothiols, protein sulfhydryl and mixed disulfides and (iii) levels of CoQ, vitamin E and vitamin C. The aminothiols status and albumin-associated carbonyl content of plasma will be determined at different times during treatments (Aim 4) to determine whether or not plasma markers of oxidative stress/damage are useful predictors of the effects of antioxidant supplementation on cognitive/psychomotor performance. These studies will provide specific information about the nature of antioxidant regimens most likely to be beneficial against brain aging and will identify the ages at which benefits should be expected. Moreover, they will improve understanding of the neurological consequences of antioxidant supplementation that are most critical to the beneficial effects and may identify clinically useful biological markers predictive of successful treatment.

描述（由申请人提供）：内源性抗氧化剂维生素E、维生素C和辅酶Q（CoQ）被认为在维持细胞氧化还原状态和保护细胞免受氧化损伤方面具有显着的相互作用。拟议的项目将确定这些化合物在以两种和三种组合方式补充时，可以在多大程度上相互作用，从而改善或预防小鼠的功能性大脑衰老。在一项实验（目标 1）中，将在晚年开始补充抗氧化剂组合，此时大脑功能已经存在。一系列行为测试将用于评估抗氧化剂补充方案逆转与年龄相关的认知功能（联想学习、工作记忆和空间学习）丧失以及感觉和精神运动功能（听觉和体感）丧失的能力。反应能力、反应时间、协调性、平衡性、肌肉力量）。如果在出现与年龄相关的脑功能障碍之前开始补充抗氧化剂，则将使用相同的一系列行为测试来确定抗氧化剂补充方案是否可以防止功能丧失（目标2）。为了确定抗氧化方案的有益效果是否取决于其减少氧化应激/损伤的能力（目标 3），前两个目标中测试的小鼠的大脑将被解剖成不同的区域，以确定：（i）对蛋白质或脂质的氧化损伤（蛋白质羰基、硫代巴比妥反应物质），(ii) 谷胱甘肽氧化还原态和氨基硫醇、蛋白质硫氢基和混合二硫化物含量的变化，以及 (iii)辅酶 Q、维生素 E 和维生素 C 的水平。将在治疗期间的不同时间测定血浆中的氨基硫醇状态和白蛋白相关羰基含量（目标 4），以确定氧化应激/损伤的血浆标志物是否是氧化应激/损伤的有用预测因子。补充抗氧化剂对认知/精神运动表现的影响。这些研究将提供有关最有可能有益于大脑衰老的抗氧化疗法的性质的具体信息，并将确定预期受益的年龄。此外，它们将增进对补充抗氧化剂的神经学后果的理解，这对于有益效果最为关键，并可能确定预测成功治疗的临床有用的生物标志物。