Zhang Xianliang, He Qiang, Huang Tao, Zhao Na, Liang Fei, Xu Bo, Chen Xianghe, Li Tuojian, Bi Jianzhong
Shandong University, Jinan, China.
College of Physical Education, Shandong Normal University, Jinan, China.
Front Aging Neurosci. 2019 Apr 5;11:78. doi: 10.3389/fnagi.2019.00078. eCollection 2019.
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 modulating microglia-mediated neuroinflammation and oxidative stress.
最近的研究表明，运动可能有助于延缓或减轻阿尔茨海默病（AD）。然而，其潜在机制尚不清楚。小胶质细胞介导的神经炎症被认为在AD的病理过程中起重要作用。本研究调查了跑步机运动对AD进展早期淀粉样前体蛋白（APP）/早老素1（PS1）小鼠的β淀粉样蛋白（Aβ）沉积和认知功能的有益影响，并主要分析了小胶质细胞介导的神经炎症。结果表明，12周的跑步机运动可保留APP/PS1小鼠的海马认知功能，并显著抑制海马中Aβ的积累。跑步机运动显著抑制神经炎症，其特征是海马中促炎因子表达显著降低，抗炎介质表达增加，这是由于活化的小胶质细胞从M1表型转变为M2表型所致。跑步机运动还减轻了氧化应激，表现为海马中丙二醛（MDA）水平显著降低，超氧化物歧化酶（SOD）和锰超氧化物歧化酶（Mn-SOD）活性显著升高。这些发现表明，跑步机运动可以有效预防早期AD进展中海马依赖性认知功能的下降和Aβ沉积，可能是通过调节小胶质细胞介导的神经炎症和氧化应激实现的。
