Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Abstract

a b s t r a c tIt is now well established, at least in animal models, that exercise elicits potent pro-cognitive and proneurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise.© 2016 Elsevier B.V. All rights reserved. Please cite this article in press as: Ryan, S.M., Kelly, Á.M., Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease. Ageing Res. Rev. (2016), http://dx

Intermittent metabolic switching, neuroplasticity and brain health

“…Interestingly, in the latter study, daily TRF lessened Aβ and tau pathologies, whereas ADF did not, suggesting that ADF protects neurons against synaptic dysfunction and cognitive deficits despite the presence of pathological Aβ and tau. As reviewed recently, aerobic exercise regimens counteract Aβ pathology and improve cognition in AD mouse models 140 .…”

Moderate‐ to high‐intensity exercise does not modify cortical β‐amyloid in Alzheimer's disease

“…However, the issue of an effect on soluble versus plaque forms of Aβ ties directly into an additional perspective, namely, the timing of the intervention. Across animal studies, there seems to be a trend toward exercise being more effective in reducing Aβ and plaque formation, the earlier in the disease process it is initiated [72]. This also coincides with the pathophysiological process when soluble Aβ, but not plaques, may predominate.…”

“…In one animal study, a brief 10‐day intervention using wheel running led to a decrease in Aβ and APP mRNA, indicating target engagement, although the number of plaques did not decrease [76]. The shortest intervention tested in animal models that was able to modify Aβ lasted around three months [72]. The intensity of the exercise intervention may also affect the ability of the intervention to modify Aβ.…”

Altered neurogenesis in mouse models of Alzheimer disease

“…Transgenic AD mouse models have been extensively studied with respect to exercise-mediated effects on deposition of amyloid-b (Ab) peptides and the impact on hippocampal neurogenesis and cognitive function has been repeatedly described (reviewed in ref. 9).…”