[1]郭一静,蒋林,张钐钐,等.跑步运动对APP/PS1小鼠内侧前额叶皮质及其小胶质细胞的作用[J].陆军军医大学学报(原第三军医大学学报),2022,44(09):862-873.
 GUO Yijing,JIANG Lin,ZHANG Shanshan,et al.Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice[J].J Amry Med Univ (J Third Mil Med Univ),2022,44(09):862-873.
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跑步运动对APP/PS1小鼠内侧前额叶皮质及其小胶质细胞的作用(/HTML )
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
44卷
期数:
2022年第09期
页码:
862-873
栏目:
神经科学
出版日期:
2022-05-15

文章信息/Info

Title:
Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice
作者:
郭一静蒋林张钐钐朱琳周春妮张蕾肖倩何琦杨浩李静邓宇辉晁凤蕾唐勇
重庆医科大学基础医学院组织学与胚胎学教研室
Author(s):
GUO Yijing JIANG Lin ZHANG Shanshan ZHU Lin ZHOU Chunni ZHANG Lei XIAO Qian HE Qi YANG Hao LI Jing DENG Yuhui CHAO Fenglei TANG Yong

Department of Histology and Embryology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China

关键词:
阿尔茨海默症跑步内侧前额叶皮质小胶质细胞CD68A&beta
Keywords:
Alzheimer&rsquos disease running medial prefrontal cortex microglia CD68 A&beta
分类号:
R165; R322.81; R745.7
文献标志码:
A
摘要:

目的研究跑步锻炼对阿尔茨海默症(Alzheimer’s disease,AD)模型小鼠内侧前额叶皮质(medial prefrontal cortex,mPFC)的体积变化、淀粉样β蛋白(amyloid beta protein,Aβ)和小胶质细胞的作用。方法 将10月龄雄性APP/PS1转基因AD小鼠以简单随机法分为AD跑步组(给予为期4个月的主动跑步干预)和AD对照组,同时设相同月龄的雄性非转基因小鼠为正常对照组(AD对照组、正常对照组不做处理)。Morris水迷宫评估小鼠的空间学习和记忆能力;Y迷宫评估小鼠的工作记忆和参考记忆能力;体视学三维定量检测小鼠mPFC的体积和小胶质细胞(IBA1+)的总数;运用免疫荧光多重标记和激光共聚焦定量小鼠mPFC内活化小胶质细胞(CD68+/IBA1+)的数量、细胞面积和突起数量,Aβ斑块的数量和面积, IBA1+细胞内Aβ斑块的面积及其与Aβ斑块总面积的比值。结果AD跑步组和正常对照组在Morris水迷宫和Y迷宫中的表现明显优于AD对照组;AD 对照组 mPFC 的体积较正常对照组显著性减小(P<0.05),而 AD 跑步组 mPFC 的体积较 AD 对照组显著性增大(P<0.01);AD对照组mPFC内IBA1+细胞和CD68+/IBA1+细胞较正常对照组显著增多(P<0.05)。AD跑步组mPFC内IBA1+细胞和CD68+/IBA1+细胞较AD对照组显著性增多(P<0.05);AD跑步组mPFC内Aβ斑块总面积及平均面积较AD对照组显著性减小(P<0.05);Aβ周围的IBA1+细胞和CD68+/IBA1+细胞数量,mPFC内单个小胶质细胞及CD68+/IBA1+细胞的平均面积、IBA1+细胞内Aβ斑块的面积及其与mPFC内Aβ斑块的总面积的比值较AD对照组显著增多(P<0.05)。结论跑步运动能够增加mPFC内CD68+小胶质细胞的数量,减少Aβ的沉积,延缓mPFC的萎缩,进而改善APP/PS1转基因AD小鼠空间学习和记忆能力以及工作和参考记忆能力。

Abstract:

ObjectiveTo investigate the effects of running on the volume change of medial prefrontal cortex (mPFC), as well as amyloid beta protein (Aβ) and microglia in mPFC in mouse model of Alzheimer’s disease (AD). MethodsMale APP/PS1 transgenic AD mice aged 10 months were randomly divided into AD running group (AD Run, given active running intervention for 4 months ) and AD control group (AD Ctrl), while non-transgenic mice at the same age were set as normal control group (Ctrl). The mice from the AD Ctrl and Ctrl groups received no treatment. Morris water maze test was used to evaluate the abilities of spatial learning and memory of mice, and Y maze test was adopted to assess the working memory and reference memory in the mice. The volume of mPFC and the total number of microglia (IBA1+cells) in the mPFC were quantified with stereological methods. The number of activated microglia (CD68+/IBA1+ cells) in the mPFC, cell body area, and process number of microglia, number and area of Aβ plaques, and area of Aβ plaques in IBA1+ microglia were quantitatively measured by immunofluorescence multiple labeling and laser confocal microscopy, and the ratio of area of Aβ plaques in IBA1+ microglia to the total area of Aβ plaques was calculated. ResultsThe AD Run group and Ctrl group performed better than the AD Ctrl group in Morris water maze and Y maze tests. The volume of mPFC was significantly less in the AD Ctrl group than the Ctrl group (P<0.05), while that of the AD Run group was obviously larger than that of the AD Ctrl (P<0.01). The AD Ctrl group had greatly larger numbers of IBA1+ cells and CD68+/IBA1+ cells in the mPFC than the Ctrl group (P<0.05), whereas the AD Run group had much larger numbers of those cells than the AD Ctrl group (P<0.05). The total and average area of Aβ plaques in the mPFC was greatly diminished in the AD Run group than the AD Ctrl group (P<0.05). In addition, the AD Run group also presented larger numbers of IBA1+ cells and CD68+/IBA1+ cells around Aβ, larger average body area of single microglia and CD68+/IBA1+ cells, and elevated area of Aβ plaques in IBA1+ cells, along with its ratio to the total area of Aβ plaques in mPFC improved (P<0.05). ConclusionRunning exercise increases the number of CD68+ microglia in the mPFC, reduces the Aβ plaques, delays the atrophy of mPFC, and thus improves the spatial learning and memory abilities as well as working memory and reference memory in APP/PS1 transgenic AD mice.  

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更新日期/Last Update: 2022-05-05