青春期慢性社交挫败应激致小鼠认知功能障碍及内侧前额叶皮质髓鞘损伤

Adolescent chronic social defeat stress induces cognitive dysfunction and myelin insult in medial prefrontal cortex of mice

目的:探讨青春期慢性社交挫败应激对小鼠认知功能及髓鞘发育的影响。方法:34只青春期雄性BALB/c小鼠随机分为对照组和应激组,应激组接受2周慢性社交挫败应激,对照组不接受任何应激。应激结束后,迷盒实验检测小鼠执行功能、短期记忆及长期记忆;Western blot法检测内侧前额叶皮质中髓鞘碱性蛋白(MBP)表达水平;免疫组化检测少突胶质细胞、增殖细胞及小胶质细胞数量。结果:迷盒实验显示,应激组小鼠在检测短时记忆的T3测试和检测长时记忆T4测试中的潜伏期分别为(300.0±0.0)s和(297.8±7.0)s,均长于对照组[分别为(212.4±94.9)s和(190.3±119.3)s],差异均有统计学意义(均P<0.05)。应激组小鼠内侧前额叶皮质中MBP表达水平较对照组降低[(3.06±1.17)vs(4.67±0.85),P<0.05],而在海马区的表达差异没有统计学意义(P>0.05)。应激组和对照组内侧前额叶皮质中的少突胶质细胞、增殖细胞及小胶质细胞的数量差异均无统计学意义(均P>0.05)。应激组小鼠在应激结束后体重低于对照组,肾上腺质量高于对照组,差异均具有统计学意义(均P<0.001)。结论:青春期慢性社交挫败应激导致小鼠内侧前额叶皮质髓鞘及记忆功能损伤。

Objective: To investigate the effects of chronic social defeat stress in adolescence on cognitive function and myelin development in mice. Methods: Thirty-four adolescent male BALB/c mice were randomly divided into a control group and a stress group. The stress group received 2 weeks of chronic social defeat stress, and the control group did not receive any stress. After the stress, the executive function, short-term memory and long-term memory were detected by puzzle box test;the expression of myelin basic protein(MBP) was detected by Western blot;the number of oligodendrocytes, proliferating cells and microglia in medial prefrontal cortex was detected by immunohistochemistry. Results: The puzzle box test showed that the incubation periods of the mice in the stress group on the T3 test for detecting short-term memory and the T4 test for detecting long-term memory were(300.0±0.0) s and(297.8±7.0) s, respectively, which were longer than those of the control group [respectively(212.4±94.9)s and(190.3±119.3) s], the differences were statistically significant(all P<0.05). The expression level of MBP in the medial prefrontal cortex of mice in the stress group was lower than that in the control group [(3.06±1.17) vs(4.67±0.85), P<0.05)], but the expression difference in the hippocampus was not statistically significant(P>0.05).There was no statistically significant difference in the numbers of oligodendrocytes, proliferating cells, and microglia in the medial prefrontal cortex between the stress group and the control group(all P>0.05). The weight of the mice in the stress group was lower than that of the control group after the end of the stress, and the weight of the adrenal glands was higher than that of the control group. The difference was statistically significant(all P<0.001). Conclusion: Adolescent chronic social defeat stress induces cognitive dysfunction and myelin insult in medial prefrontal cortex of mice.