AUTHOR=Zhang Xianliang , He Qiang , Huang Tao , Zhao Na , Liang Fei , Xu Bo , Chen Xianghe , Li Tuojian , Bi Jianzhong TITLE=Treadmill Exercise Decreases Aβ Deposition and Counteracts Cognitive Decline in APP/PS1 Mice, Possibly via Hippocampal Microglia Modifications JOURNAL=Frontiers in Aging Neuroscience VOLUME=11 YEAR=2019 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00078 DOI=10.3389/fnagi.2019.00078 ISSN=1663-4365 ABSTRACT=

Recent studies have suggested that exercise may be beneficial for delaying or attenuating Alzheimer’s disease (AD). However, the underlying mechanisms were not clear. Microglia-mediated neuroinflammation is suggested to play an important role in the pathology of AD. The present study investigated the beneficial effects of treadmill exercise on amyloid-β (Aβ) deposition and cognitive function in amyloid precursor protein (APP)/PS1 mice in the early stage of AD progression and microglia-mediated neuroinflammation was mainly analyzed. The results demonstrated that 12 weeks of treadmill exercise preserved hippocampal cognitive function in APP/PS1 mice and substantially suppressed Aβ accumulation in the hippocampus. Treadmill exercise significantly inhibited neuroinflammation, which was characterized by a remarkably reduced expression of pro-inflammatory factors and increased expression of anti-inflammatory mediators in the hippocampus, resulting from a shift in activated microglia from the M1 to M2 phenotype. Treadmill exercise also attenuated oxidative stress presented by a marked reduction in methane dicarboxylic aldehyde (MDA) level and dramatically elevated SOD and Mn-SOD activities in the hippocampus. These findings suggest that treadmill exercise can effectively prevent the decrease in hippocampal-dependent cognitive function and Aβ deposits in early AD progression possibly via modulating microglia-mediated neuroinflammation and oxidative stress.