A growing body of literature suggests oxidative stress mediates Alzheimer’s disease pathology. Amyloid beta plaque accumulation directly damages mitochondria, increases oxidative stress, and can eventually lead to mutation-signaled apoptotic events. Within the brain, these events can manifest severe behavioral deficits in learning and memory. Nrf2, a transcription factor that regulates antioxidant enzyme production, has become a target of interest in neurodegeneration with evidence of protection against amyloid beta toxicity and learning deficits. Protandim, a Nrf2 activator, contains a variety of phytochemicals. This study sought to determine if Protandim could prevent amyloid beta mediated learning and memory deficits associated with Alzheimer’s disease. Wild type and 5xFAD transgenic mice were either supplemented with Protandim or a vehicle and assessed in the Morris-water maze to measure spatial learning and memory and the active avoidance box to assess associative learning. No effect of Protandim was observed in either paradigm, however an expected effect of genotype was observed in Morris water maze learning trials in which transgenic mice performed markedly worse. Transgene effects observed in spatial tasks and lack thereof in classical conditioning paradigms indicate that the onset of plaque-mediated deficits vary by brain region. While findings from this study did not validate previous literature on antioxidant activity, time constraints of treatment and limitations indicate further research must be conducted and holds the potential to yield findings in support of the current study’s hypothesis.
Stavnezer, Amy Jo
Crookshanks, Michael T., "Rescuing Alzheimer’s Disease-Related Memory Impairment Through Nrf2 Activation" (2019). Senior Independent Study Theses. Paper 8600.
Bachelor of Arts
Senior Independent Study Thesis
© Copyright 2019 Michael T. Crookshanks