Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice
Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice
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DOI：
10.1523/eneuro.0068-22.2022
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发表时间：
2022-04
期刊：
影响因子：
3.4
通讯作者：
Hibiki Okamura;Shinnosuke Yasugaki;Haruka Suzuki-Abe;Y. Arai;Katsuyasu Sakurai;Masashi Yanagisawa;Hotaka Takizawa;Y. Hayashi
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文献类型：
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作者：
Hibiki Okamura;Shinnosuke Yasugaki;Haruka Suzuki-Abe;Y. Arai;Katsuyasu Sakurai;Masashi Yanagisawa;Hotaka Takizawa;Y. Hayashi
理解压力对大脑功能的长期影响对于理解抑郁症的机制至关重要。BALB/c小鼠品系对应激具有高度敏感性，因此是抑郁症的有效模型。然而，反复社交失败应激（SDS）对BALB/c小鼠的长期影响尚不清楚。在这里，我们研究了在随后的两周内重复SDS对雄性BALB/c小鼠的影响。一些失败的小鼠立即表现出社交回避，而焦虑样行为只在后期才明显。此外，失败的小鼠分为两组的基础上的社会回避，即回避和nonavoidant小鼠。在两周内，每个个体的回避或不回避特征并不固定。此外，我们开发了一种半自动化的方法来分析c-Fos在小鼠大脑中的表达，以研究重复SDS对大脑活动的影响超过两个星期后结束的压力暴露。在社会互动之后，与对照组小鼠相比，失败小鼠的几个脑区的c-Fos表达减少。这些脑区之间的c-Fos表达的相关性，除了内侧前额叶皮层（mPFC）和中央杏仁核（CeA），在失败的小鼠中增加，表明同步性增加。值得注意的是，c-Fos在外侧缰（LHb）的表达是不同的小鼠表现出社会回避后立即重复SDS和那些表现出社会回避只在后期。这些观察为社会压力对行为和大脑活动的长期影响提供了深入的见解。
Abstract Understanding the long-term effects of stress on brain function is crucial for understanding the mechanisms of depression. The BALB/c mouse strain has high susceptibility to stress and is thus an effective model for depression. The long-term effects of repeated social defeat stress (SDS) on BALB/c mice, however, are not clear. Here, we investigated the effects of repeated SDS in male BALB/c mice over the subsequent two weeks. Some defeated mice immediately exhibited social avoidance, whereas anxiety-like behavior was only evident at later periods. Furthermore, defeated mice segregated into two groups based on the level of social avoidance, namely, avoidant and nonavoidant mice. The characteristic of avoidance or nonavoidance in each individual was not fixed over the two weeks. In addition, we developed a semi-automated method for analyzing c-Fos expression in the mouse brain to investigate the effect of repeated SDS on brain activity more than two weeks after the end of the stress exposure. Following social interaction, c-Fos expression was reduced in several brain regions in the defeated mice compared with control mice. The correlation of c-Fos expression among these brain areas, with exception of the medial prefrontal cortex (mPFC) and central amygdala (CeA), was increased in defeated mice, suggesting increased synchrony. Notably, c-Fos expression in the lateral habenula (LHb) was different between mice that exhibited social avoidance from immediately after the repeated SDS and those that exhibited social avoidance only at later periods. These observations provide insight into the long-term effects of social stress on behavior and brain activity.