Stereological Investigation of the Effects of Treadmill Running Exercise on the Hippocampal Neurons in Middle-Aged APP/PS1 Transgenic Mice
Stereological Investigation of the Effects of Treadmill Running Exercise on the Hippocampal Neurons in Middle-Aged APP/PS1 Transgenic Mice
复制标题
跑步机跑步运动对中年APP/PS1转基因小鼠海马神经元影响的体视学研究
DOI：
10.3233/jad-171017
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Tang, Yong
中科院分区：
文献类型：
--
作者：
Chao, Fenglei;Jiang, Lin;Tang, Yong
如果保持体力活动，阿尔茨海默病（AD）期间认知能力下降的风险可以降低;然而，这种有益效果背后的特定神经事件仍然不确定。为了定量研究跑步运动对中年AD受试者影响的神经事件，将12个月大的雄性APP/PS1小鼠随机分配到对照组或跑步组，并将年龄匹配的非转基因同窝小鼠用作野生型组。AD跑步组小鼠进行四个月的跑步机跑步方案（常规和中等强度）。Morris水迷宫检测大鼠空间学习记忆能力。用硫磺素S染色和免疫组化观察海马淀粉样斑块。海马体积，神经元的数量，和新生细胞（BrdU+细胞）在海马的数量进行了估计，使用体视学技术和新生神经元进行了观察，使用双标记免疫荧光。在中年APP/PS1小鼠的海马CA 1区和齿状回（DG）的神经元损失和缺陷的神经发生和新的神经元的存活在DG观察。跑步运动可改善中年APP/PS1小鼠的空间学习记忆能力，减少海马淀粉样斑块，延缓神经元丢失，诱导神经元发生，促进DG新生神经元存活。运动诱导的DG内神经元保护和成年神经发生可能是AD小鼠空间学习和记忆能力改善的重要结构基础的一部分。
The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice.