| dc.description.abstract | Alzheimer's disease (AD) is a neurodegenerative disease currently affecting 5.7 million Americans, and the disease prevalence is expected to rise to 14 million by 2050. One characteristic pathological marker of AD is plaques of amyloid-beta (A-beta) peptides, which corresponds with a deterioration of memory and cognition in patients afflicted with AD. As mice do not naturally form A-beta plaques, our lab utilizes the 5xFAD transgenic mouse, a model of familial AD, wherein genetically modified human genes introduced into the mouse genome allow for the study of AD pathology. While several environmental factors impact AD pathology, stress has been found to exacerbate production of A-beta in different transgenic mouse models. Thus, the first goal of the current project was to determine if a social stressor, isolation stress, would increase levels of A-beta, number of A-beta plaques, and cognitive deficits in 5xFAD+ mice in comparison to group-housed controls. In addition, the second goal of this project was to determine whether the hypothesized stress-induced increase in A-beta plaques could be prevented through exposure to physical exercise alone, or to exercise and an enriched environment throughout the period of isolation. One subset of 5xFAD+ and 5xFAD- two-month-old mice were housed in group-housed and isolated conditions. An additional subset of 5xFAD+ two-month-old mice were housed in isolation, housed in isolation with an exercise wheel, or housed in isolation with an exercise wheel and an enriched environment. After 3 months of group-housing or isolation, cognition was assessed through contextual fear conditioning, and brains were collected for hippocampal A-beta plaque counts and quantification of A-beta levels. Extended isolation stress significantly increased the number of hippocampal plaques and cognitive deficits in 5xFAD+ mice. However, these effects of social isolation were not prevented by exercise or an enriched environment in the 5xFAD+ mice. As AD prevalence continues to increase, understanding how stress impacts the onset and progression of AD is critical to develop therapeutic practices to alleviate disease progression. | |
