Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice
Oliver K Fuller, Emma McLennan, Casey L. Egan, Nimna Perera, Lauren V. Terry, Jae Pyun, Mariana de Mendonca, Guilherme Defante Telles, Benoit Smeuninx, Emma L. Burrows, Ghizal Siddiqui, Darren J. Creek, John W. Scott, Michael A. Pearen, Pamali Fonseka, Joseph A. Nicolazzo, Suresh Mathivanan, Anthony J. Hannan, Grant A. Ramm, Martin Whitham, Mark A. Febbraio
Abstract
Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.