Department of Biological Sciences, Konkuk University, Seoul, South Korea.
FASEB J. 2021 Dec;35(12):e22041. doi: 10.1096/fj.202101287R.
Mood disorders are more prevalent and often reported to be more severe in women; however, little is known about the underlying mechanisms of this sexual prevalence. To gain insight into the functional differences in female brains in response to stress, we systemically compared brain activation in male and female C57BL/6N mice after acute stress exposure. We measured c-Fos expression levels in 18 brain areas related to stress responses after a 3-h long restraint stress and found that activation was sexually dimorphic in several brain areas, including the nucleus accumbens, ventral tegmental area, nucleus reuniens, and medial part of the lateral habenula. Moreover, stress-activated a substantial number of cells in the medial prefrontal cortex, amygdala, and lateral part of the lateral habenula; however, the levels of activation were comparable in males and females, suggesting that the core stress responding machineries are largely shared. Pearson correlation analysis revealed several interesting connections between the analyzed areas that are implicated in stress responses and depression. Overall, stress strengthened intra-circuitries in the hippocampus, amygdala, and prefrontal cortex in female mice, whereas more longer-range connections were highlighted in stressed male mice. Our study provides a highly valuable neuroanatomical framework for investigating the circuit mechanism underlying the higher vulnerability to depression in women.
心境障碍在女性中更为普遍，且常被报告更为严重；然而，对于这种性别差异的潜在机制知之甚少。为了深入了解女性大脑在应对压力时的功能差异，我们系统比较了急性应激暴露后雄性和雌性 C57BL/6N 小鼠的大脑激活情况。我们测量了 18 个与应激反应相关的脑区在 3 小时束缚应激后的 c-Fos 表达水平，发现多个脑区的激活存在性别二态性，包括伏隔核、腹侧被盖区、 reunions 核和外侧缰核的内侧部。此外，应激激活了内侧前额叶皮质、杏仁核和外侧缰核的外侧部中的大量细胞；然而，雄性和雌性之间的激活水平相当，这表明核心应激反应机制在很大程度上是共享的。Pearson 相关分析揭示了在与应激反应和抑郁相关的分析区域之间存在几种有趣的连接。总的来说，应激增强了雌性小鼠海马体、杏仁核和前额叶皮质中的回路，而应激雄性小鼠中则强调了更多的长程连接。我们的研究为研究女性对抑郁症更高易感性的潜在电路机制提供了一个非常有价值的神经解剖学框架。
