Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice

Yijing GUO; Lin JIANG; Shanshan ZHANG; Lin ZHU; Chunni ZHOU; Lei ZHANG; Qian XIAO; Qi HE; Hao YANG; Jing LI; Yuhui DENG; Fenglei CHAO; Yong TANG

doi:10.16016/j.2097-0927.202110032

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Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice

Neurosciences | 更新时间：2026-01-09

- Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice
- Journal of Army Medical University Vol. 44, Issue 9, Pages: 862-873(2022)
- 作者机构：
  
  400016 重庆，重庆医科大学基础医学院组织学与胚胎学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81871073);the General Program of Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0125)
- DOI：10.16016/j.2097-0927.202110032
  CLC： R165;R322.81;R745.7
- Received：09 October 2021，
  
  Revised：2021-11-11，
  
  Published：15 May 2022
- 稿件说明：
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Yijing GUO, Lin JIANG, Shanshan ZHANG, et al. Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice[J]. Journal of Army Medical University, 2022, 44(9): 862-873.
DOI：

Yijing GUO, Lin JIANG, Shanshan ZHANG, et al. Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice[J]. Journal of Army Medical University, 2022, 44(9): 862-873. DOI： 10.16016/j.2097-0927.202110032.

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(

0.05)，而AD跑步组mPFC的体积较AD对照组显著性增大(

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(

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(

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(

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(

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

Objective

To 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).

Methods

Male 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 us

ed 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.

Results

The 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 (

0.05)

while that of the AD Run group was obviously larger than that of the AD Ctrl (

0.01). The AD Ctrl group had greatly larger numbers of IBA1

cells and CD68

/IBA1

cells in the mPFC than the Ctrl group (

0.05)

whereas the AD Run group had much larger numbers of those cells than the AD Ctrl group (

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 (

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 (

0.05).

Conclusion

Running exercise increases the number of CD68

micr

oglia 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.

关键词

Keywords

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