Page 11 - 南京医科大学自然版

第45卷第10期 王乙淼，王 泽，佘雨竹，等. 丰富环境改善5×FAD小鼠社会行为障碍［J］.
2025年10月 南京医科大学学报（自然科学版），2025，45（10）：1375-1385 ·1379 ·

表型产生影响，但是改善了小鼠的社交障碍。 2.3 EE 改善 5×FAD 小鼠 mPFC 的髓鞘结构完整
2.2 EE改善5×FAD小鼠的Aβ负荷与胶质细胞活化 性，但未影响突触相关指标
6E10 免疫荧光染色和硫磺素染色结果均显示 有研究表明，mPFC是识别记忆、情绪调控以及
3 月龄的 5×FAD 小鼠 mPFC 中已经有 Aβ斑块沉积， 社会行为的调控的关键脑区 ［19-20］ 。本研究探讨了
而EE组Aβ斑块沉积有所改善（图2A~D）。在6E10 EE 对 5×FAD 小鼠 mPFC 神经元数量以及突触的影
阳性 Aβ斑块周围存在 GFAP 阳性星形胶质细胞和 响。结果显示两组动物 mPFC NeuN 阳性神经元数
Iba1 阳性的小胶质细胞的分布。与 SE 组相比，EE 量没有显著差异（图3A、B）。PSD⁃95和SYP的免疫
组小鼠 mPFC 中 GFAP 阳性的星形胶质细胞面积百 组织化学以及免疫印迹实验证实EE并未影响mPFC
分比和Iba1阳性的小胶质细胞面积百分比均减少， 突触蛋白的表达和分布（图3C~F，图4A~C）。与此一
提示 EE 降低了 5×FAD 小鼠 mPFC 中星形胶质细胞 致，透射电镜与定量分析结果显示 EE 对 5×FAD 小
和小胶质细胞的活化（图2E~H）。 鼠 mPFC 脑区的突触相关指标无显著性影响，两组

A
SE Y⁃maze Open⁃field test Elevated plus maze Social test Immunohistochemistry
4 weeks Immunofluorescence
5×FAD
Electron microscopy
2⁃month⁃old EE
Day 1 Day 2 Day 3 Day 4 Western blotting
B C
Y⁃maze 50 15 Elevated plus maze 50 20
SE Other EE New （%） SE EE （%） 40 15
Time spent 40 5 Open arm Time spent 20 5
arm arm 45 Entering number 10 30 Entering number 10
10
35 0 0 0
Start arm Close arm
SE EE SE EE SE EE SE EE
D
The open field 20 20 6 150
（%） 4 number
SE EE 15 15 100
Time spent 10 5 Entering number 10 5 0 Defecation 2 Travelling speed （mm/s） 50

0 0 0
SE EE SE EE SE EE SE EE
E Sociability Empty Center Stranger⁃1 F Social novelty Stranger⁃1 Center Stranger⁃2
P=0.001
P=0.048
SE EE 80 P=0.004 SE EE 60 P=0.002 P=0.009
（%） 60 P < 0.001 （%） 40

Empty Stranger⁃1 Time spent 40 Stranger Stranger Time spent 20
20
⁃1
⁃2
0 0
SE EE SE EE
A：Schematic diagram of the experimental design. Two⁃month⁃old 5×FAD mice were randomly divided into two groups and housed under different
conditions for four weeks. Behavioral tests were conducted sequentially：Y⁃maze test on Day 1，open field test on Day 2，elevated plus maze test on Day
3，and social interaction test on Day 4. Pathological analyses，including immunofluorescence，immunohistochemistry，electron microscopy，and Western
blotting，were performed after behavioral assessments. B：On the left is a heatmap of the movement trajectories of the mice during the Y⁃maze test.
On the right are the statistical analyses of the percentage of time spent and the number of entries into the novel arm. C：On the left is a heatmap of the
movement trajectories of the mice during the elevated plus maze test. On the right are the statistical analyses of the percentage of time spent and the
number of entries into the open arms. D：On the left is a heatmap of the movement trajectories of the mice during the open field test. On the right are the
statistical analyses of the percentage of time spent and the number of entries into the central area，fecal pellet counts，and movement speed. E：On the
left is a heatmap of the movement trajectories of the mice during the sociability test in the three⁃chamber social interaction experiment. On the right is
the statistical analysis of the percentage of time spent in each chamber during the sociability test. F：On the left is a heatmap of the movement trajectories
of the mice during the social memory test in the three⁃chamber social interaction experiment. On the right is the statistical analysis of the percentage of
time spent in each chamber during the social memory test. Compared with the SE group mice（n=10）.
图1 EE对5×FAD小鼠的行为影响
Figure 1 Effects of EE on behavioral outcomes in 5×FAD mice