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Dose-dependent Effects of Voluntary Exercise on Physiology, Behavior, and Pathology in Mouse Models of Healthy Aging and Alzheimer's Disease

Posted on:2018-05-19Degree:Ph.DType:Dissertation
University:State University of New York at Stony BrookCandidate:Robison, Lisa SuzanneFull Text:PDF
GTID:1444390002995491Subject:Neurosciences
Abstract/Summary:
Exercise has been shown to be protective against cognitive decline in aging and risk for dementias including Alzheimer's Disease (AD). Exercise has also been shown to have several beneficial effects on the brain and behavior in mouse models of healthy aging and AD; however, studies examining the effects of exercise on cerebral amyloid angiopathy [CAA; the accumulation of amyloid-beta (Abeta) in the cerebrovasculature] are lacking. CAA may be uniquely susceptible to cardiovascular interventions due to the nature of the pathology. Additionally, most studies assessing exercise in mice only test a single "dose" of exercise -- unlimited running wheel access. This intervention results in very high levels of exercise not akin to the amount that an average person would perform, highlighting the need to test the efficacy of smaller "doses". In the current study, the dose-dependent effects of voluntary aerobic exercise were assessed in wild-type (WT) mice and Tg-SwDI (TSDI) mice, a transgenic mouse model of CAA that exhibits behavioral deficits associated with vascular Abeta pathology. Various "doses" of exercise intervention [0h ("Sedentary"), 1h, 3h, 12h access to running wheel] were assessed from 4 to 12 months of age for effects on physiology, behavior, and pathology. WT and TSDI mice ran similarly and did not exhibit motor dysfunction or altered levels of anxiety or sociability, though TSDI animals did appear to exhibit slower rates of exploration. TSDI mice exhibited significant Abeta pathology and increased expression of pro-inflammatory cytokines compared to WT mice, as well as altered cortical thickness and measures of the vasculature. Exercise was generally effective at improving motor function and reducing anxiety-like behavior. Dose-dependent effects of exercise on behavior were apparent on other tasks, and varied based on mouse strain. Findings also suggest that exercise may dose-dependently affect several physiological measures and reduce fibrillar amyloid and inflammation in the brain. Interestingly, it was found that exercise may alter the balance between soluble and insoluble Abeta levels in TSDI mice, which was associated with behavioral changes, without affecting the balance between Abeta 40 and 42 levels.
Keywords/Search Tags:Exercise, Behavior, TSDI mice, Dose-dependent effects, Aging, Pathology, Mouse, Abeta
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