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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG027353-05
Application #
7847476
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Mackiewicz, Miroslaw
Project Start
2006-08-15
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
5
Fiscal Year
2010
Total Cost
$249,821
Indirect Cost
Name
University of North Texas
Department
Pharmacology
Type
Other Domestic Higher Education
DUNS #
110091808
City
Fort Worth
State
TX
Country
United States
Zip Code
76107
Mock, J Thomas; Chaudhari, Kiran; Sidhu, Akram et al. (2017) The influence of vitamins E and C and exercise on brain aging. Exp Gerontol 94:69-72
Shetty, Ritu A; Ikonne, Uzoma S; Forster, Michael J et al. (2014) Coenzyme Q10 and ?-tocopherol reversed age-associated functional impairments in mice. Exp Gerontol 58:208-18
Sumien, Nathalie; Chaudhari, Kiran; Sidhu, Akram et al. (2013) Does phytoestrogen supplementation affect cognition differentially in males and females? Brain Res 1514:123-7
Shetty, Ritu A; Forster, Michael J; Sumien, Nathalie (2013) Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age (Dordr) 35:1821-34