Effects of Exercise and an Enriched Environment on Cognition and A Plaque Load following Isolation Stress in 5xFAD Mice
Calcagno, A.1, Peterman, J. L.1, White, J. D.1, Baroni, N.1, Eimerbrink, M. J.1, Hagen, C.2, Boehm, G. W.1 & Chumley, M. J.2 1Department of Psychology, Texas Christian University; 2Department of Biology, Texas Christian University
The prevalence of Alzheimer's disease (AD), a neurodegenerative disease characterized by the pathological hallmarks of amyloid beta (A) plaques and neurofibrillary tangles, continues to increase, even as its etiology remains elusive. Further, stress afflicts a considerable portion of the world's population, and, may exert similar effects to those of cardiovascular disease (CVD) and stroke, increasing disease risk and worsening disease outcomes. One such disease heavily impacted by stress is Alzheimer's disease. Indeed, stress has been found to exacerbate A production in transgenic mouse models of AD. We hypothesized that a social stressor, isolation stress, would exacerbate A production and increase the number of A plaques in 5xFAD+ transgenic mice in comparison to group-housed controls. Further, we hypothesized that isolated, 5xFAD+ animals would have a learning deficit in a contextual fear-conditioning (CFC) paradigm, a hippocampus-dependent memory task. Additionally, we aimed to determine whether pathological or behavioral impacts of isolation stress could be prevented through exposure to exercise alone or to exercise and an enriched environment throughout the isolation period. Two-month old 5xFAD+ and 5xFAD- animals were isolated or group housed for two and three months. An additional subset of 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 extended isolation or group housing, cognition was assessed utilizing CFC, following which animals were perfused and a brain hemisphere was collected for sectioning and staining for plaques, while the hippocampus was removed from the other hemisphere and A was quantified. Two and three months of isolation stress significantly increased the number of plaques in the hippocampus of 5xFAD+ mice. Isolated animals also displayed significant cognitive deficit in CFC. Understanding how stress impacts the onset and progression of AD is critical, as human populations continue to endure significant stress over the lifespan.
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