Treadmill Exercise Promotes Microglial β-Amyloid Clearance and Prevents Cognitive Decline in APP/PS1 Mice

Growing evidence has demonstrated that treadmill exercise is beneficial to increase beta-amyloid (A beta) clearance and protect against Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. Recently, microglia dysfunction leading to A beta clearance impairment is proved an important mechanism for later A beta deposition and AD pathogenesis. The present study aimed to confirm the effect of exercise on A beta deposition and to investigate the role of microglia in exercise-induced A beta reduction. In the present study, 3-month-old male APPswe/PS1dE9 (APP/PS1) mice and C57BL/6 wild-type mice were randomly divided into sedentary (SED) or exercise (EX) group, twelve mice in each group. Mice in exercise groups were subjected to ran on a treadmill for 3 months, 5 days/week. Afterwards, the spatial learning and memory, hippocampal fibrillar A beta deposits and microglial functions were determined by Morris water maze task, methoxy-X04 staining as well as in vivo and in vitro assays, respectively. The results showed that 3 months of treadmill exercise largely prevented spatial learning and memory decline and alleviated hippocampal methoxy-X04-positive fibrillar A beta deposits in APP/PS1 mice. Moreover, treadmill exercise partly restored microglial A beta degradation and clearance in the hippocampus, which was impaired in APP/PS1 mice. However, the impaired microglial phagocytosis in APP/PS1 mice was not altered after 3 months of treadmill exercise intervention. These findings demonstrate that 3 months of treadmill exercise alleviates hippocampal A beta deposition and restores spatial learning and memory in APP/PS1 mice, partly by promoting microglial A beta degradation and clearance. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.