Brain aging and antioxidant supplementation

大脑老化和抗氧化剂补充

• 批准号: 7618379
• 负责人: MICHAEL J. FORSTER
• 金额: $ 28.04万
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618379
• 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; 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态和细胞保护中具有显着相互作用。拟议的项目将确定这些化合物可以在两种和三向组合中补充时可以改善或预防小鼠的功能性脑老化的程度。在一个实验中（AIM1），在已经存在脑功能障碍的年龄时，将启动对抗氧化剂组合的补充。一系列行为测试将用于估计抗氧化剂补充方案的能力，可以逆转与年龄相关的认知功能损失（联想学习，工作记忆和空间学习），以及感官和心理动物功能的损失（听觉和体验性的响应能力，反应时间，反应时间，均衡，平衡，平衡，平衡，肌肉）。如果在与年龄相关的脑功能障碍之前开始补充剂，则将使用相同的行为测试来确定抗氧化剂补充方案是否可以防止功能损失（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氨基硫醇，蛋白质亚硫烯醇和混合二硫化物以及COQ，维生素E和维生素C的水平。氨基硫醇的状态和与白蛋白相关的血浆碳含量将在处理过程中的不同时间确定（目标4），以确定是否有用的氧化和损害的等化症状效果。认知/精神运动表现。这些研究将提供有关最有可能对脑衰老有益的抗氧化剂方案的性质的特定信息，并将确定应预期受益的年龄。此外，他们将提高对补充抗氧化剂的神经系统后果的理解，这对有益作用最为重要，并且可以鉴定出可预测成功治疗的临床有用的生物学标志物。