Distinguished Master's Thesis Award
2016 Robert and Kathryn Augustine
Distinguished Master's Thesis Award Winner
Eric Hendricks, Master of Science in Biological Sciences, earned EIU's top research honor for his master's thesis titled, The Impact of Aging and Estrogen Therapy on Synaptic Mitochondrial Bioenergetics in an Alzheimer's Mouse Model.
Britto Nathan, Ph.D., professor of biological sciences and Michael Menze, Ph.D., associate professor of biological sciences, served as faculty mentors.
The award is named for, and supported by, former dean of the Graduate School, Dr. Robert Augustine, and his wife, Kathy, an EIU alumna.
Mitochondrial dysfunction is a recognized pathological symptom of Alzheimer’s disease (AD). One of the known risk factors for the development of AD is the inheritance of a specific genotype a lipid transporting protein, apolipoprotein E (apoE). How apoE contributes to the development and progression of AD is poorly understood. The purpose of this study was to determine if a relationship exists between mitochondrial dysfunction and genetic predisposition to AD via apoE.
Mitochondrial bioenergetics was evaluated by measuring oxygen consumption using the OROBOROS Oxygraph-2k in nerve cell terminals (synaptosomes) isolated from WT (C57BL/6J) and apoE KO (Apoetn1Unc) mice. Enzymatic activity of succinate dehydrogenase (SDH) and citrate synthase (CS) activity was also assayed to help elucidate the bioenergetic profile of isolated synaptosomes. Since AD develops with age, mitochondrial function was studied in both young (4-6 months old) and old (12-22 months old) mice. Additionally, estrogen therapy was utilized as a possible therapeutic to prevent mitochondrial dysfunction. Our results revealed a dramatic increase in oxygen consumption from young estrogen treated apoE KO for all respiration parameters, whereas, a minimal effect was observed in WT mice. In addition, old Sham mice had significantly higher oxygen consumption rates compared to young Sham mice for most all permeabilized parameters in both WT and apoE KO mice. Estrogen had no effect on oxygen consumption in old mice, but estrogen treated old apoE KO mice had significantly higher SDH activity compared to its Sham. We speculate that increases in mitochondrial quantity in young apoE KO mice and old Sham mice were due to estrogen and reactive oxygen species induced mitochondrial biogenesis, respectively. Our data suggests that predisposition of AD via apoE is not an underlying source of mitochondrial abnormalities; however, the effectiveness of estrogen as a neuro-therapeutic may be dependent upon an individual’s age and apoE genotype.