Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology

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

“…Wheel running and treadmill training both prove effective methods of exercise, and indeed cognitive gains are observed in aged animals following just three weeks of exercise (Parachikova et al, 2008), however, reduction in A␤ plaque number (along with cognitive and neurogenic gains) was only observed after ten weeks of running (Tapia-Rojas et al, 2016) and thus it appears that a minimum term of one month upwards of voluntary running should be considered to affect A␤ pathology. Beyond this, there doesn't appear to be an upper limit for duration of voluntary running with reductions in p-Tau and improvements in spontaneous alternation observed following nine months of running (Belarbi et al, 2011). However, one must consider the intensity of exercise training when training durations are extended over a long term timecourse.…”

“…Six weeks of wheel running had no effect on numbers of GFAP + astrocytes and Iba-1 + microglia in APP SWE /PS-1 E9 mice (Xu et al, 2013). Similarly, nine months of voluntary wheel running failed to alter the number of GFAP + astrocytes and also had no effect on mRNA expression of IL-1␤, TNF-␣ and CD68 in the hippocampus of THY-Tau22 mice (Belarbi et al, 2011). Presently, the few studies in which inflammation has been examined and the mixed results which have been obtained make it difficult to draw solid conclusions about potential antiinflammatory effects of exercise.…”

“…Thus far, Tapia-Rojas et al (2016) report a reduction in GFAP + cells following ten weeks wheel running in five month old APP SWE /PS-1 E9 mice while Ke et al (2011) observed reduced microglial activation in adult and aged mice following five weeks of treadmill running; Parachikova et al (2008) demonstrated a reduction in mRNA expression of interleukin-11 (IL-11) and the chemokines chemokine ligand 1 (CXCL1) and chemokine ligand 12 (CXCL12) following three weeks of wheel running in 15-19 month old Tg2576 mice. In contrast, neither treadmill exercise nor wheel running reduced microglial and astrocyte activation along with pro-inflammatory cytokine mRNA expression in APP SWE /PS-1 E9 and THY-Tau22 mice respectively (Belarbi et al, 2011;Xu et al, 2013). To date, exercise-mediated effects have been observed in both young and aged mice.…”

“…Beneficial effects were observed following just three weeks of voluntary wheel running (Nichol et al, 2007) up to nine months of wheel running (Belarbi et al, 2011). Exercising mice on treadmills also resulted in gains when mice were trained for five weeks (Ke et al, 2011) up to five months (Bo et al, 2014;Zhao et al, 2015).…”

“…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).…”