• Role of antioxidant supplementation and exercise regimen in handling oxidative stress from natural PM2.5 exposure due to boreal forest fire

      Witkop, Jacob J.; Dunlap, Kriya; Duffy, Lawrence; Reynolds, Arleigh (2019-05)
      Particulate matter 2.5 (PM2.5) exposure induces oxidative stress that causes many negative health outcomes such as cancer, cardiovascular disease and neurodegenerative disease. Research shows that dietary antioxidants and an up-regulated endogenous antioxidant response from exercise play key roles in the antioxidant defense against oxidative stress. This study is the first to use an animal model to investigate the cumulative effects of using lifestyle interventions of antioxidant supplementation (Arthrospira platensis) and exercise regimen on the antioxidant response before, during, and after ambient PM2.5 exposure. In a two-factorial, longitudinal design, sled dogs (n=48) were divided into four groups (exercise and supplemented, exercise, supplemented, and control) to (1) test the effects of exercise and antioxidant regimen on antioxidant response after one month of implemented exercise and supplementation protocol and (2) measure the antioxidant response of all groups during and after a natural forest fire event in 2015. Commercial assays for Total antioxidant Power (TAP) and the enzymatic antioxidant Superoxide Dismutase (SOD) were used as markers for the total antioxidant response and the endogenous response at all time points. During the forest fire, SOD was increased 5-10-fold over pre/post-exposure levels in all groups suggesting potential implication for using SOD as a marker for the acute response to environmental stress. TAP was increased in the exercise groups after one month of exercise protocol implementation, demonstrating the cytoprotective increase of antioxidants after repeated exercise.
    • Role of dietary fat and supplementation in modulating neurodegenerative pathology in two animal model systems

      Maulik, Malabika; Bult-Ito, Abel; Taylor, Barbara E.; Duffy, Lawrence; Kuhn, Thomas; Dunlap, Kriya (2018-12)
      Neurodegenerative disorders are progressive conditions that worsen over time and results in death of neurons. Parkinson's disease (PD) is a prevalent example of one such age-related disease, which is characterized by movement disorder (ataxia) and/or cognitive disability (dementia). Pathologically, PD is characterized by a toxic accumulation of α-synuclein protein in the midbrain leading to degeneration of the dopaminergic neurons. The etiology of PD is intricate, and the cause is attributed to genetic mutations and environmental factors like insecticides or heavy metals. Moreover, treatment options are limited and often aimed at treating the symptoms rather than the actual disease progression. Using the nematode model of Caenorhabditis elegans, I examined the effect of Alaskan bog blueberry (Vaccinium uliginosum) on α-synuclein overexpression and how such indigenous natural treatment can modulate key molecular targets like sirtuins, which are proteins involved in regulating cellular processes including aging, death and their resistance to stress. The impact of extrinsic factors like dietary fat on PD pathology has been sparsely explored and the molecular basis of such changes is not known. Through my thesis research, I also further investigated the influence of fat metabolism on key hallmarks of PD: α-synuclein overexpression and dopaminergic degeneration in the nematode model. Finally, I studied the interaction of dietary fat (normal, low and high fat) and Alaskan blueberry supplementation on metal induced neurotoxicity model of Mus musculus. Our results highlight the beneficial properties of Alaskan blueberries in combating proteotoxic stress and inflammation in both animal models. They also reiterate the benefit of low fat diet, on its own or in combination with supplementation in improving several PD-like molecular features and how consuming high fat can mask such health promoting outcomes. The current thesis work therefore, provides a foundation for further exploration of neurobiological changes associated with consumption of natural products and different diets and how such alterations can be extrapolated to humans.