• Effects of methylmercury and theaflavin digallate on adipokines in mature 3t3-l1 adipocytes

      Chauhan, Shubhangi; Duffy, Lawrence; Drew, Kelly; Dunlap, Kriya (2019-05)
      Diabetes is a contributor to morbidity across the globe and is often associated with obesity, metabolic syndrome and other inflammatory diseases associated with aging. In addition to genetic and lifestyle factors, environmental factors such as metals and persistent organic pollutants may increase the severity or lower the threshold of these conditions. In cell culture, methylmercury is toxic to adipocytes and may impact the adipokine secretions. In this study, I determined the effects of different concentrations of theaflavin digallate on methylmercury exposed 3T3-L1 adipocytes in cell culture. Secretions of resistin, adiponectin and lipid peroxidation product, 4-HNE were monitored using ELISA assays from Day 18 to 28. Cell morphology was assessed over the period of ten days and on day 28 was observed using Lipid (Oil Red O) staining. Results showed that exposure to methylmercury increased the levels of resistin and adiponectin as well as 4-HNE when compared to the control cells. Methylmercury treated cells resulted in smaller and highly clumped lipid droplets. These results suggest that methylmercury induces reactive oxygen species leading to development of an inflammatory response. Theaflavin digallate reduced the impact of methylmercury by restoring the morphology and secretion patterns of adiponectin, resistin and 4-HNE. With this enhanced signaling model other anti-inflammatory agents could be tested at this biochemical level eventually leading to studies in animal models.
    • Quality of life for Alaskan individuals with FASD and their families

      Dow, Brenda S.; Ehrlander, Mary; Boylan, Brandon; Anahita, Sine; Rivkin, Inna (2019-05)
      Fetal alcohol spectrum disorder (FASD) is a lifelong disability caused by prenatal exposure to alcohol. The effects of FASD include a range of physical, mental, behavioral, and learning disabilities. These disabilities impact quality of life, not only for the affected individual, but for family members. The effects from FASD ripple into schools, the correctional system, and throughout rural and urban communities. Although there are no reliable statistics available on FASD in Alaska, many professionals in the field believe Alaska to have the highest rate of FASD in the United States. This research has explored the ways in which prenatal exposure to alcohol affects quality of life for Alaskan individuals and their families. For this study, I have defined quality of life as the multi-faceted evaluation of the individual's personal experiences and life satisfaction, including health, psychological and social indicators. Since the identification of fetal alcohol syndrome (FAS) and FASD, many studies have analyzed the effects of prenatal alcohol exposure, as well as possible interventions. Few studies have investigated how prenatal alcohol exposure affects the individual's quality of life and even fewer studies have analyzed how raising one or more children with FASD affects the family. To address the gap in the literature, this research applied social constructivist theory and employed a qualitative design, using semi-structured interviews to explore individuals' and parents' life stories and perceptions on how FASD has affected their lives. I interviewed eight individuals with FASD and 14 adoptive or long-term foster parents. Findings indicate that FASD impacts almost every facet of the lives of both the individuals affected and their families. All individuals with FASD interviewed for this project suffered serious adverse childhood experiences in addition to their prenatal exposure to alcohol. All encountered academic and social difficulties at school. Individuals struggled in their transitions to adulthood, with some individuals needing assistance from parents or social services throughout their lifespan. Parents expressed their ongoing need for structure within the home and the continual need to advocate for suitable services for their children. They described how the ongoing stress of raising their child(ren) with FASD affected their social lives, employment and even their marriages. The perspectives and insight of these individuals with FASD and their parents can provide other family members, service providers and legislators a better understanding of how FASD affects quality of life and assist decision makers in making informed choices on how to best provide expanded or improved supportive services to these individuals and families whose everyday struggles go largely unrecognized by the general public.
    • 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.