The Effect of Late-Life Antioxidant Supplementaion on Brain Function

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dc.contributor.advisorForster, Michael J.
dc.contributor.committeeMemberSumien, Nathalie
dc.contributor.committeeMemberSingh, Meharvan
dc.creatorShetty, Ritu A.
dc.date.accessioned2019-08-22T21:26:17Z
dc.date.available2019-08-22T21:26:17Z
dc.date.issued2007-10-01
dc.date.submitted2013-10-23T07:50:06-07:00
dc.description.abstractShetty, Ritu A., The effect of late-life antioxidant supplementation on brain function. Doctor of Philolosophy (Biomedical Sciences), October, 2007, 229 pp., 5 tables, 18 figures, bibliography, 284 titles. Purpose: Aging is associated with mild to moderate loss in brain function over time. These functional losses are thought to involve reversible changes disrupting important cellular signaling processes. One of the theories that proposes to explain the reversible losses of function is the ‘oxidative stress’ hypothesis of aging. According to the oxidative stress hypothesis, there is an inherent cellular imbalance between production of oxidants and antioxidative defenses that increases with age and that leads to an increase in oxidative damage to macromolecules that are involved in crucial cell functions. Previous studies have established a link between these cellular changes associated with aging and the impairments in cognitive and psychomotor function. Further it has also been suggested that dietary interventions can modulate the level of oxidative stress, reducing oxidative damage and perhaps even ameliorate age-related dysfunction. Most interventions have been implemented relatively early in life and maintained until old age. However, the current studies were based on the rationale that interventions initiated in late-life could potentially lower oxidative damage and thereby alter cellular components responsible for functional impairments. Methods: In study I, separate groups of young (4 months) and old mice male C57BL/6 (18 months) were fed a control diet or a diet supplemented with low (105 mg/kg/day) or high (368 mg/kg/day) concentrations of CoQ10 for a period of 15 weeks. After 6 weeks on the diets, the mice were subjected to a battery of age-sensitive behavioral tests. In study II, separate groups of male C57BL/6 young mice aged 3-4 months and old mice 17-18 months (total of n=124) were fed ad libitum either a control diet (cyclodextrin in base diet), or the same diet supplemented with D- α-tocopheryl acetate (Toc) (200 mg/kg body wt/day), or with CoQ10 (148 mg/kg body wt/day) or a diet containing a combination of CoQ and Toc (200 mg/kg body wt/day + 148 mg/kg body wt/day) for a period of 13-14 weeks. In both studies mice were subjected to a battery of behavioral tests that required utilization of various component of memory and learning and sensorimotor reflexes. Results: In study I, low CoQ10 failed to improve cognitive and psychomotor function in old mice. However, the high CoQ10 marginally helped the old mice to navigate in the swim maze task with greater efficiency than control mice but did not affect their performance in probe trials. Conversely, the high CoQ10 diet selectively impaired the spatial performance in young mice in probe trials. The results from study I indicated that intake of CoQ10 initiated in late-life had minimal beneficial effects on behavior function. In study II, an age-associated decline of behavioral functioning was observed; however CoQ10 treatment failed to improve the performance of mice in any of the age-sensitive tests. Moreover, young mice supplemented with a high CoQ diet performed poorly in the probe trial in a swim maze task, suggesting a possible deleterious effect. The results from study II indicated that there was a significant improvement in performance of old mice in the coordinated running and the learning ability in discriminated avoidance task when supplemented with Toc or with a combination of CoQ10 and Toc. Conclusions: In conclusion, these studies suggest that benefits of single antioxidant supplementation when initiated late in life are limited; however dietary supplementation with a combination of antioxidants has a greater impact in reversing age-related decline in behavioral function.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29332
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectBehavioral Neurobiology
dc.subjectBiochemistry
dc.subjectBiological Factors
dc.subjectBiology
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectChemical Actions and Uses
dc.subjectChemicals and Drugs
dc.subjectClinical Epidemiology
dc.subjectCommunity Health and Preventive Medicine
dc.subjectComparative Nutrition
dc.subjectDevelopmental Biology
dc.subjectDevelopmental Neuroscience
dc.subjectLife Sciences
dc.subjectMedical Neurobiology
dc.subjectMedicine and Health Sciences
dc.subjectMolecular and Cellular Neuroscience
dc.subjectNatural Products Chemistry and Pharmacognosy
dc.subjectNervous System
dc.subjectNeuroscience and Neurobiology
dc.subjectNutrition
dc.subjectOther Neuroscience and Neurobiology
dc.subjectOther Nutrition
dc.subjectPharmacy and Pharmaceutical Sciences
dc.subjectSystems and Integrative Physiology
dc.subjectLate-life
dc.subjectantioxidant supplementation
dc.subjectbrain function
dc.subjectaging
dc.subjectoxidative stress
dc.subjectcellular imbalance
dc.subjectmice
dc.subjectswim maze
dc.titleThe Effect of Late-Life Antioxidant Supplementaion on Brain Function
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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