Neuroprotective effects of bioactive compounds (resveratrol and genistein) in various mouse models
Type of DegreePhD Dissertation
Nutrition, Dietetics and Hospitality Management
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Obesity is a complex disease which has adverse effects on various organ including liver, heart and brain. It was shown that obesity is a significant risk factor for developing type 2 diabetes, heart disease and neurodegenerative disease such as Alzheimer’s disease (AD). The relationship between obesity, type 2 diabetes and cognitive impairment is important, considering the increased aging population in whom cognitive dysfunction will carry huge individual, financial and societal burdens. Bioactive compounds such as carotenoids, isoflavones, and polyphenols have received increased attention due to their antioxidant, anti-inflammatory, anti-aging, and anti-cancer properties. These effects make them promising candidates for the prevention and treatment of obesity, type 2 diabetes and AD. This study is mainly focusing on resveratrol and genistein. Promoting regular exercise is also an effective non-pharmacological approach that prevent the progression of metabolic and neurodegenerative diseases. Therefore, the first objective of this study is to examine the neuroprotective effects of chronic resveratrol supplementation with exercise training in the 3xTg-AD mouse model. Our observations suggest that resveratrol ameliorated neuroinflammation, decreased accumulation of amyloid beta (A) oligomers, improved levels of neurotrophic factors and synaptic markers, inhibited apoptosis, autophagy and ubiquitination in the brain of the 3xTg-AD mouse. Exercise improved few markers related to neuroprotection, but when combined with resveratrol treatment, the benefits achieved were as effective as resveratrol treatment alone. Secondly, we would like to investigate the beneficial effects of genistein on diabetes-induced brain damage. Leptin deficient (ob/ob) mice and high-fat/high-sugar (HFHS) diet-induced diabetic mice were chosen. Our results suggest that genistein improved brain insulin signaling, increase neurotrophic support and alleviated AD-related pathology in the brain of ob/ob mice. In the brain HFHS diet-fed mice, genistein supplementation coupled with exercise training decreased the accumulation of A, improved the expression of neurotrophic factor as well as ameliorated apoptosis. Moreover, it was suggested that the neuroprotective effects of genistein are associated with its capability to bind the estrogen receptor. Further cell culture study was conducted, and the results demonstrate that the anti-apoptotic actions of genistein were selectively mediated by estrogen receptor in PC12 cells following high glucose and palmitate exposure.