title: Long-term treadmill exercise improves spatial memory of male APPswe/PS1dE9 mice by regulation of BDNF expression and microglia activation.
abstract: Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer's disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of β-amyloid, brain-derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of β-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P < 0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation of β-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P > 0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect.
authors.affiliation: School of Physical Education, Lingnan Normal University, Zhanjiang 524048, China ; Equal contribution.
authors.forename: J Y
authors.initials: JY
authors.lastname: Xiong
authors.affiliation: School of Physical Education, Lingnan Normal University, Zhanjiang 524048, China ; Equal contribution.
authors.forename: S C
authors.initials: SC
authors.lastname: Li
authors.affiliation: Library of Mudanjiang Medical University, Mudanjiang 157011, China ; Equal contribution.
authors.forename: Y X
authors.initials: YX
authors.lastname: Sun
authors.affiliation: School of Physical Education, Lingnan Normal University, Zhanjiang 524048, China ; Equal contribution.
authors.forename: X S
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325200, China.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Dong
authors.affiliation: Laboratory of Physiological Science, Guangdong Medical University, Dongguan 523808, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University, Dongguan 523808, China ; Institute of Aging Research, Dongguan Scientific Center, Guangdong Medical University, Dongguan 523808, China.
authors.forename: X R
authors.initials: XR
authors.lastname: Sun
keywords: Alzheimer's disease; brain-derived neurotrophic; exercise; factor; mice; microglia