Abstract
Physical exercise has been suggested to reduce the risk of developing Alzheimer’s disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse model of AD did not affect levels of soluble amyloid beta (Aβ), synaptic proteins or cognitive function. In this follow-up study, we investigate whether running could impact other pathological aspects of the disease, such as insoluble Aβ levels, the neuroinflammatory response and non-cognitive behavioral impairments. We investigated the effects of 24 weeks of voluntary wheel running in female 5xFAD mice (n = 30) starting at 2–3 months of age, before substantial extracellular plaque formation. Running mice developed hindlimb clasping earlier (p = 0.009) compared to sedentary controls. Further, running exacerbated the exploratory behavior in Elevated plus maze (p = 0.001) and anxiety in Open field (p = 0.024) tests. Additionally, microglia, cytokines and insoluble Aβ levels were not affected. Taken together, our findings suggest that voluntary wheel running is not a beneficial intervention to halt disease progression in 5xFAD mice.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia, affecting around 30 million people worldwide (WHO 2016)
We have recently shown that 6 months of voluntary running in 5xFAD mice did not result in any beneficial effects on soluble Aβ-levels, synaptic protein levels or cognitive behavior[24]
We recently reported on the appearance of neuroinflammation in this model before extracellular amyloid deposition[28] and the important role of pro-inflammatory microglial galectin-3 in development of pathology and behavioral deficits[33]
Summary
Alzheimer’s disease (AD) is the most common form of dementia, affecting around 30 million people worldwide (WHO 2016). The 5xFAD strain is a mouse model with a fast development of AD pathology, showing accumulation of extracellular Aβ plaques and signs of neuroinflammation as early as 2–3 month of age[25,26,27,28]. Prior studies in other AD models suggest that exercise may reduce neuroinflammation by reducing microglial activation and levels of pro-inflammatory cytokines[31,32]. We recently reported on the appearance of neuroinflammation in this model before extracellular amyloid deposition[28] and the important role of pro-inflammatory microglial galectin-3 in development of pathology and behavioral deficits[33]. In light of the pathological importance of myeloid cells in AD, the aim of this study was to further investigate the effects of 6 months of voluntary wheel running on neuroinflammation and non-cognitive behavior in the 5xFAD model
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