Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer's disease

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

“…A␤ plaque number (Liu et al, 2013), levels of A␤40/42 (Walker et al, 2015), tau phosphorylation (Um et al, 2011) and p-Tau + cells (Tapia-Rojas et al, 2016) were all reduced following exercise (both voluntary and forced) across a number of models. However, it is also evident from certain studies that age (and thus degree of pathology) affects the ability of exercise to ameliorate some of the pathological features of AD.…”

“…Voluntary wheel running and treadmill running both reduce A␤ plaque number, soluble A␤ protein and tau phosphorylation (Belarbi et al, 2011;Cho et al, 2015;Tapia-Rojas et al, 2016;Um et al, 2011;Yuede et al, 2009;Zhao et al, 2015). Most recently, evidence was published demonstrating a doseresponse effect for treadmill exercise-mediated reduction of soluble A␤40 and A␤42 protein, with high intensity runners having the greatest reduction in A␤40/42 levels (Moore et al, 2015).…”

“…Finally, in the APP23 mouse model of amyloidosis, ten days of voluntary wheel running reduced cell survival in six month old mice but increased neuronal differentiation (Mirochnic et al, 2009). Furthermore, several studies have reported increased expression of synaptic plasticity-related proteins, key growth factors and transcription factors that are associated with exercise-mediated effects on hippocampal neurogenesis such as synaptophysin and postsynaptic density protein 95 (PSD-95) (Cho et al, 2015;Revilla et al, 2014), BDNF (Cho et al, 2015;Um et al, 2011), nerve growth factor (NGF) (Um et al, 2011), glialderived neurotrophic factor (GDNF) (Revilla et al, 2014), cAMP response element-binding protein (CREB) (Um et al, 2011) and SIRT1 (Revilla et al, 2014). From the few studies to date that have examined exercise-induced effects on hippocampal neurogenesis in AD mouse models, it is clear that neurogenic deficits can be effectively modulated by this intervention.…”

“…Other studies provide evidence for a curative effect of exercise. Training of 24 month old Tg-NSE/hPS-2 mice on a treadmill for three months was found to reduce hippocampal A␤42 protein and tau phosphorylation as well as improve performance of the mice in the MWM (Koo et al, 2013;Um et al, 2011). A number of other studies also provide evidence for exerciseinduced amelioration of cognitive function in mice in which AD pathology is deemed to be advanced but disappointingly have not included any data on exercise-induced alterations on typical AD pathologies (Marlatt et al, 2013;Rodriguez et al, 2011).…”

Effect of treadmill exercise on PI3K/AKT/mTOR, autophagy, and Tau hyperphosphorylation in the cerebral cortex of NSE/htau23 transgenic mice

“…These were achieved due to positive changes in brain health, such as increased brain volume, generating neuronal cells and growth factors, and promoting cerebral vasculogenesis [25][26][27]. Moreover, another study reported that exercise can reduce the expressions of Aβ-42 and hyperphosphorylated tau, which are pathological markers of Alzheimer's disease [28][29][30]. Many studies have shown that exercise might reduce AP and NTF, which are the pathological features of Alzheimer's disease, but studies investigating the effect of exercise on molecular signaling pathways that might reduce the hyperphosphorylation and aggregation of tau protein, or determining whether exercise might control mTOR signaling pathway and autophagy-related proteins are lacking.…”