Browsing by Subject "Antioxidants"
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Item EFFECTS OF APOE GENOTYPE, ANTIOXIDANTS AND EXERCISE ON MOTOR AND COGNITIVE FUNCTION(2013-04-12) Chaudhari, KiranPurpose: The ɛ4 allele of apolipoprotein E (ApoE) has been associated with increased risk for development of late-onset Alzheimer's disease (AD). To prevent appearance of brain dysfunction, a healthy lifestyle, such as exercising and eating antioxidants, is often recommended. Physical activity has been shown to have an allele-specific beneficial effect on cognition in humans and rodents. Antioxidant therapy is often suggested to improve brain function, as increased oxidative stress has been correlated with brain dysfunction, especially in ɛ4 carriers. Health conscious individuals are likely to combine exercise with antioxidant intake to increase protection, however recent studies have indicated a negative interaction of these two factors. In some cases, antioxidant intake abolished the beneficial effects of exercise. Our study aimed at determining the nature of the interaction between exercise and antioxidants on functional outcomes in a model of increased AD risk. Methods: Young male and female mice, expressing the human ApoE3 or E4, were placed under one of the treatment: Sedentary/control diet (SedCon), Sedentary /antioxidant-rich diet (Vitamins E and C; SedEC), Exercise/control diet (EXCon), Exercise/ antioxidant-rich diet (EXEC), for 8 weeks prior to behavioral testing. Behavior testing includes running co-ordination (rotorod), spatial learning and memory (Morris Water Maze)and discriminative avoidance and cognitive flexibility (T maze). Results: In a coordination test, the E3 mice performed better than the E4 mice, and a significant improvement was observed with the ExEC treatment in males E3 and females E4. Better spatial learning was detected with EXEC in E3 females but not in E4. In males EX impaired learning index in E3 males. In active avoidance acquisition session, learning performance was improved with EX and EXEC treatment in E3 male, and with EXCon treatment in female E4, whereas cognitive flexibility was improved in both male and female in E3 by all the treatments but not in E4. Conclusions: These results in young mice provide an indication that genotype and sex are critical determinants in the functional outcomes of the treatment.Item The Neuroprotective Efficacy of Antioxidants Against In Vitro Models of Oxidative Stress and Their Theoretical Application Via Intravitreal Injection Encapsulated in Nanoparticles(2010-05-01) Ondricek, Amber J.; Jamboor VishwanathaThe purpose of this study was to explore the possibility of utilizing antioxidants to mitigate oxidative stress induced apoptosis related to neurodegenerative diseases such as glaucoma. Our hypothesis is that in diseases related to an imbalanced redox status, whatever the primary cause may be, the loss of function may be prevented by antioxidants at the level of alleviating oxidative burden and preventing apoptotic signaling events. Application of these antioxidants to the site of injury can be improved using nanoparticle delivery methods. We have done work to characterize a model of mitochondrial associated oxidative stress induced cell death and obtained neuroprotective profiles on a group of antioxidants using this model. We have found that estrogens and phytoestrogens, as well as thiol containing antioxidants, function well as neuroprotectants in our in vitro model. Nanoparticle delivery of these models is a promising intervention and we therefore did work to optimize the characteristics of encapsulating one of these antioxidants, N-acetyl cysteine, in Poly(lactic-coglycolic acid) nanoparticles, which can be localized to the retina. Intravitreal injection of these particles is the preferred delivery route to retinal cells and has not been fully explored. We provide evidence to suggest that the intravitreal injection of nanoparticles is not detrimental to an animal’s vision. Taken together, the results of our experiments suggest that antioxidants remain a promising intervention in diseases related to mitochondrial associated oxidative stress, and that these drugs, when encapsulated in nanoparticles, can be delivered to the retina via intravitreal injection without deleterious side effects.